The Viral NBME Typhoon

A segmented RNA virus is causing severe diarrhea within the children at your local school. What could've been used to prevent this outbreak?

A promising rotavirus vaccine made from a human/rhesus reassortant virus was approved in 1998. It performed well in pre-clinical studies, but major adverse causes of intussusception forced its withdrawal from use. New rotavirus vaccines are now licensed and available for use in the United States. These include RotaTeq which is a live, oral pentavalent rotavirus vaccine based on a bovine strain and contains 5 human-bovine reassortants. Rotarix is a monovalent attenuated human strain vaccine.

An infleunza epidemic occurs in your community, despite there being a record 90% vaccination rate. What mechanism of influenza allows for this?

Antigenic drift results from point mutations that provide for antigen variation on the viral surface. Antigens shift results when two infecting viruses within the same cell reassert genomic segments in HA or NA genes. This creates a new virus and may lead to a pandemic.

What are the trigger words for Flaviviruses and Togaviruses?

Arbovirus vector dead-end host reservoir host encephalitis rubella congenital rubella syndrome MMR vaccine

Describe the development of the annual influenza vaccine.

At the end of each influenza virus season, the CDC determines which viruses were most prevalent during, and especially, at the end of the season. This analysis is what determines the recommendation for the viral types to be used in the vaccine for the upcoming year. See the web site (http:/www.cdc.gov/ncidod/diseases/flu/weekly.htm). Viruses are grown in embryonated eggs. Hence, anyone allergic to egg protein should not be given the vaccine. The viruses are purified and inactivated with formalin to create a vaccine that is then delivered by injection.

Describe the trigger words for parvovirus

B19 erythrovirus fifth disease erythema infectiosum aplastic anemia slapped cheek disease

As an infectious disease specialist, you are consulted to treat a 19 year old kidney transplant recipient. He is currently taking Abatacept and anti-CD3 in order to prevent tissue rejection. He is currently suffering from extreme exhausting and swollen lymph nodes. You diagnose mononucleosis. The patient responds to cidofovir treatment. -Describe the spread of disease in the host, host-to-host transmission, and epidemiology of the infecting agent.

CMV may persist in leukocytes, but also infects most other cells. Secretory cells become infected and release virus into their secretions. CMV can be transmitted transplacentally, via blood, semen or organ transplants, and in other secretions. CMV can cause a large number of different diseases, but rarely in an immunocompetent individual.

A young boy comes to your office with acute onset of fever, headache, confusion, and seizures. The current date is September 1st. -What viral cause should be on the differential?

Differential diagnosis must be made from a large number of infections and diseases. Cases of encephalitis in late summer should be tested for LaCrosse IgM antibodies especially in areas where the disease is endemic.

As an infectious disease specialist with the CDC, you are called in to investigate an outbreak of disease among ten grade-school aged boys two months after their school field-trip to a woods-camp. All of the boys are feeling extremely sluggish, and one of them has began to develop extremely swollen tonsils. One night prior, the tonsillitis patient was admitted to the hospital and intubated due to airway obstruction. They started him immediately on IV corticosteroids in order to decrease inflammation. He is in stable condition. At the woods camp, the ten boys all stayed in the same cabin, and they admit to sharing the same water bottle. The patient in the hospital admits to being sexually active. -What cellular receptor does the virus which is infecting these boys utilize in order to enter host cells? -What sequelae can this virus cause?

EBV enters B lymphocytes via CD21 (CR2) and epithelial cells of the nasopharynx and establishes latency in memory B cells. EBV can "immortalize" B lymphocytes and is associated with B cell lymphomas and nasopharyngeal carcinoma.

The Department of Homeland Security is investigating a plot to infect the US water supply with an artificially developed agent of Creutzfeldt-Jakob Disease (CJD). This would cause a serious long-term threat to the American public. Describe its pathogenesis.

Experimental evidence suggests that prions are composed primarily of an abnormally folded cellular protein (the prion protein; PrP) encoded by the host gene, PRNP. The abnormal protein accumulates in the brain, due to its high stability and resistance to proteases. Prion replication is dependent upon the expression of the normal prion protein (PrPC) by host cells which is subsequently converted to the abnormal form (PrPSc =PrP-scrapie), by PrPSc template-induced conformational refolding of PrPC. The sequence of the host PRNP gene influences prion disease susceptibility. In particular, susceptibility to vCJD is significantly influenced by the amino acid residue at position 129. Homozygous M/M are susceptible, whereas V/V or heterozygous M/V exhibit a barrier to infection.

One of your patient's at the free clinic presents with general ill-health, loss of appetite, nausea, vomiting, body aches, mild fever, and dark urine, and then progression to development of jaundice. History reveals to you that he is a male prostitute. Describe the replication of the infecting agent.

HBV is a small, enveloped virus with a partially double-stranded circular DNA genome which encodes a reverse transcriptase. A circular RNA is synthesized as an intermediate for reverse transcription of single HBV DNA circles which become partially double-stranded after encapsidation.

A 23 year old AIDS patient presets to you with Kaposi's Sacroma. -A virus from what group is infecting your patient?

HHV8 is a gammaherpesviridae virus. It is a Kaposi's sarcoma-associated virus. Common disease in AIDS patients but also immunocompetent individuals from certain geographic regions. Opportunistic Disease.

What are the trigger words for HIV?

HIV CD4 receptor CD4 lymphocytes gp120 CCR5 CXCR4 Protease inhibitors reverse transcriptase inhibitors AIDS viral load opportunistic infections

A 15 year old female presents with an acute respiratory distress syndrome, hemorrhage, and renal failure. RT-PCR indicates viral RNA in her lung tissue. Her mother tells you that she has been nursing an injured squirrel back to health. -Describe the means of transmission of the infecting agent.

Hantavirus, a member of the bunyavirus family, has been found in the United States to be the cause of a severe respiratory illness that is often fatal. The natural host for hantavirus is rodents. Transmission to humans is thought to occur after exposure to rodent excreta. Hantavirus pulmonary syndrome is a clinical result from Sin Nombre virus and others like it. In the past, hanta viral infection was mainly associated with hemorrhagic fever and renal abnormalities (Hantaan virus).

A patient comes into the ER with extreme abdominal pain and jaundice. Several hours later he is rushed into surgery due to internal hemorrhage, and the surgeon notes severe necrosis of the liver. He expires on the table. Postmortem serum analysis indicates very high HBsAg. -What was special about this infection that made it so lethal?

Hepatitis D is defective and requires the presence of HBV to replicate. -When it coinfects with HBV it has around 90% fatality.

Forty patients come down with severe jaundice several weeks after eating at a Chinese buffet. Fecal-food contamination from unwashed hands is determined to be the cause. Three of those infected end up expiring, and all of them were pregnant women. -What potential viruses can cause fecal-oral hepatitis? Which one cause this outbreak?

Hepatitis E, a calici-like virus, is a major cause of water and food-borne hepatitis. It caused this outbreak, and is extremely deadly in pregnant women. Hepatitis A, a picornavirus, is the major cause of infectious hepatitis.

One of your patient's was just diagnosed with an adult T cell leukemia. Serum analysis indicates the presence of enveloped (+)ssRNA viruses. -Through what mechanism is this virus causing neoplasm?

Human T-cell lymphotropic virus type I (HTLV-I) is a human retrovirus that infects T helper cells and neurons. HTLV-I is associated with the development of adult T-cell leukemia (ATL) and is also linked to severe neurological disease. HTLV-I can induce production of interleukin-2 (IL-2) and IL-2 receptors by having the infected cell produce a viral protein known as a transactivator. HTLV-I is strongly cell associated and is transmitted by blood, sexual contact and breast feeding. The virus is endemic in Southern Japan, Central Africa and the Caribbean basin. HTLV-I is screened for its presence in the blood supply in the U.S.

One of your patient's presents with scabes and disseminated CMV infection. You order a p24 test, and a very high result is yielded. -How is the viral agent able to evade your patient's immune system? What viral genes are involved?

In addition to the standard retroviral genes, gag, pol and env, HIV encodes several genes involved in the positive and negative regulation of viral gene expression such as the tat gene, a transactivator of viral gene expression. HIV-1 Nef gene and protein decreases CD4 receptor levels to permit HIV virion release and also suppresses MHC I from the cell surface which facilitates viral escape from cytotoxic T cell response. HIV-1 viral accessory proteins Vpx, Vpu, and Vif function to counteract innate cellular restriction and immunity.

After Step One of boards, you go out on the town to "party it up." During your experience you run into a troupe of hippies while eating a 3 AM burrito at Taco Tanto's in Kent. You decide to "hang at their pad," and they give you several illicit materials to try. While smoking the "sweet Ganja" and eating "magic mushrooms," you have a transcendental experience and regress back to a past life. In your past life, you are a physician in the early 1900s, who is giving a live Vaccinia vaccine to the people in your town. Describe the presentation and transmission route of the infection that the vaccine is aimed to prevent.

Infections with most poxviruses are characterized by a rash which may form macule and papule lesions known as pox . Smallpox was once a dreaded disease, transmitted via the aerosol route, that killed and scarred many through the centuries. Smallpox has been eliminated by the use of Vaccinia virus as a vaccine. However, there is grave concern that some countries may have the smallpox virus for purposes of biological warfare.

What are the trigger words for orthomyxoviruses?

Influenza segmented genome neuraminidase hemagglutinin antigenic shift antigenic drift epidemic pandemic neuraminidase inhibitor avian influenza virus reassortment

A pandemic respiratory virus is sweeping the country. The hospital that you are rotating at has an entire ward of elderly individuals who are on respirators, because they are unable to breathe successful for themselves. The virus's genome is segmented, and contains (-)ssRNA. Describe the family and transmission of the virus. Why are there no young people on respirators?

Influenza (an orthomyxovirus) is transmitted in respiratory aerosol droplets or by contact with contaminated hands or surfaces. The virus infects the upper and lower respiratory tract. Morbidity is associated with both severe symptoms of the respiratory illness (fever, myalgias, arthralgias, rhinorrhea, cough, sore throat) as well as disease complications. Complications of influenza are most common in the extreme ages of life, both young and old, with secondary bacterial pneumonia being the most common.

What are the trigger words for the family Polyomaviridae?

JC virus BK virus PML BK nephropathy

What are some trigger words for HHV8?

Kaposi's sarcoma AIDS

A 23 year old man has headache, nausea, vomiting, fever, and stiff neck after a summer hike in the woods. CSF has normal glucose, with lymphocytic presence but no PMN presence. Patient recovered with no sequalae after 5 days. -Describe the structure and genome of the infecting agent.

LaCrosse virus, a member of the Bunyavirus family, is the most important arboviral cause of encephalitis in children in the United States. The Bunyaviridae are enveloped viruses having a spherical shape. The viral genome has three single strands of negative-sense RNA. Viral glycoprotein is on the envelope. The bunyaviruses can recombine genes by the process of genetic reassortment. Headache, drowsiness, fever, vomiting and stiff neck are the most common presenting symptoms. These may be followed by tremors, confusion, convulsions and coma. Paralysis in the extremities may occur, but is rare.

An AIDS patient presents to your with disseminated symptoms which are indicative of systemic infection. His distress ranges from respiratory to hepatic to splenic. Biopsies of his tissue show large cells with owl-eye nuclear inclusions. -What treatment regimen would you recommend for your patient?

Laboratory diagnosis of CMV is by detection of large (megalo) cells with "owl-eye" nuclear inclusions, antigen or genome (PCR) detection. FDA approved anti-CMV drugs include ganciclovir, valganciclovir, cidofovir and foscarnet.

One of your patients was just diagnosed with full blown AIDS. He has begun to develop dementia-like symptoms. What aspect of the viral agent allows for CNS involvement?

Lymphoid tissue is the principal reservoir and site of viral replication. Extra- cellular virions trapped on the surface of follicular dendritic cells can infect the CD4+ Tcellsthatmovethroughthecellclusters. HIV-infected macrophages may help maintain and extend the infection to the brain.

One of your refugee patients from Nepal comes down with an infectious disease. It starts with a fever, which gets up to 103. Soon after, it causes a cough, runny nose, and red eyes. Then a rash of tiny, red spots breaks out. It starts at the head and spreads to the rest of the body. Is this infection contagious? Is there an animal reservoir? Describe possible sequelae. Can it be prevented?

Measles is highly contagious; there is one serotype; there is no animal reservoir; inapparent infections are rare; infection confers life-long immunity. Involvement of the central nervous system is common in measles. Before the measles vaccine was developed, there were 500,000 cases annually with 400 deaths in the U.S.A. Measles virus is still a major cause of child mortality worldwide. The measles virus vaccine is attenuated and should be given to children after 15 months of age.

An AIDS patient presents to you with a small, raised skin-colored papules on his arms which have persisted for 3 months. Each lesion has a central dimple bite does not cause pain or itching. -What is the cause of this infection? How could a vaccine be developed for it?

Molluscum contagiosum is a benign epidermal tumor caused by an unclassified member of the poxvirus group. Molluscum contagiosum lesions are most commonly found on the trunk, genitalia, face, arms, back and buttocks. These lesions may be a marker for other STDs. Recombinant vaccines can be produced by using vaccinia virus as an expression vector for isolated genes from other viruses.

A 53 year old male presents to you with severe respiratory distress. Upon questioning, you discover that he had recently been spending time with his grandson, who was infected with a large, enveloped DNA virus. As a child, your patient was never infected with this virus. He is also unvaccinated against it. Within a matter of hours, your patient is on mechanical ventilation due to his rapidly deteriorating condition. -What treatment should you provide to your patient? What other member of this viral family is the treatment active against?

Passive immunization (VZIG) can be given for immediate effect. FDA-approved anti-HSV/VZV drugs include: acyclovir (HSV & VZV), penciclovir (HSV), famciclovir (HSV & VZV), valacyclovir (HSV and VZV). -Also approved, but less effective, are: vidarabine (AraA), trifluorothymidine and iododeoxyuridine. -An attenuated vaccine is available for prevention in other uninfected individuals

Describe the trigger words for adenovirus

Pharyngoconjunctivitis Keratoconjunctivitis Acute respiratory disease gastroenteritis

What are the trigger words for Prion disease?

Prion Slow virus Scrapie PrPC PrPSc Transmissible spongiform encephalopathy Creutzfeldt-Jakob Disease Kuru FFI GSS BSE CWD Amyloid plaques Gliosis Vacuolation Spongiosis

Immigrant boy from Indonesia develops fever, headache, and vomits. He refuses to take pills and drink water due to painful swallowing. Two days later he has a high fever, is delirious, becomes paralyzed, and falls into coma. He dies. Autopsy shows Negri bodies in the brain biopsy. -Describe the structure and replication of the infecting agent.

Rabies virus is a member of the family Rhabdoviridae that has a bullet-shaped structure, an envelope with a single glycoprotein and a single-stranded, negative- sense RNA genome. Rabies virus multiplies at the site of infection in the muscle and enters the nerve at neuromuscular junctions spreading to the CNS and back out to the skin and salivary glands. Depending on the site of infection, the incubation period is generally 3 to 8 weeks, yet it can be as short as 6 days and as long as 1 year.

A retrovirus is found to be oncogenic in humans, but genomic analysis is unable to find any oncogenes within the strain's genome. -Through what mechanism is it initiating cancer growth?

Retroviruses can cause tumors by either having a viral oncogene (v-onc) or by insertion next to a cellular proto-oncogene (c-onc). Viral insertion can disrupt the proto-oncogene itself or disrupt the normal transcriptional control of its activity.

What do filoviruses cause?

The Filoviruses, Marburg and Ebola, cause viral hemorrhagic fevers, hepatic degeneration, and have the highest case fatality rate of all viral infections.

As a part of a virology competition, you are given a sample to identify. In order to get the necessary points, you must accurately determine what viral family it came from. Via the use of acid testing, you are able to tell that it is acid labile. TEM analysis shows that the nucleocapsid is NOT spherical, and the envelope is NOT bullet shaped. Genetic testing shows that it is NOT a segmented genome. Animal testing confirms that it is NOT an Arbovirus, and does't cause a hemorrhagic fever. Describe the structure of the viral family you are dealing with. How does it attach to cells?

The Paramyxoviridae family includes measles virus, parainfluenza viruses, mumps virus and respiratory syncytial virus (RSV). The genome of Paramyxoviruses consists of negative sense, single-stranded linear RNA. Virion surface structures include fusion (F) glycoprotein and either hemagglutinin (H) or hemagglutinin-neuraminidase (HN). Paramyxoviruses attach to host cells via the hemagglutinin glycoprotein (HN or H) and the virion envelope fuses with the cell membrane by the F glycoprotein.

A 60 year old Japanese man has skin lesion similar to Sezary syndrome. Flower cells are detected in his blood. The diagnosis is T-cell lymphocytic leukemia. -Describe the structure of the infecting agent. What subgroups exist within its viral family?

The Retroviridae have an icosahedral protein capsid that is surrounded by a spherical-shaped envelope membrane from which viral glycoprotein projects. The virion contains two copies of a single-stranded linear RNA genome with positive sense. Also enclosed is an enzyme called reverse transcriptase and a cellular tRNA molecule which serves as a primer to initiate reverse transcription. Retroviruses are classified into three groups. The oncoviruses are tumor- producing viruses; the lentiviruses are involved in slow, chronic infections; the spumaviruses cause a distinct cytopathology without overt clinical symptoms.

As a graduate student you are doing your thesis on the causes of the "common cold." After running several assays on one of your patients, you determine that the virus does not lyse modified red blood cells which are covered by receptors consisting of immunoglobulin superfamily proteins. Also, it is unable to dock with cells that express ICAM. -What is the structure of this cause of the "common cold"? -Describe its replication

The coronaviridae have a pleomorphic spherical virion that is enveloped and has large club-shaped projections. The genome is linear, single-stranded RNA with positive sense. Human coronaviruses cause colds and generally remain localized in the upper respiratory tract. The virus elicits a poor immune response. Although the coronavirus genome is positive-sense, different size mRNA's are synthesized from a negative-sense template RNA to encode various viral proteins.

A five year old girl presents to you with a three day history of malaise. Her parents suspected that she was "down with the flu," however, her day-care sent her home today due to a lace-like rash on her face. Bacterial cultures come back negative, and you immediately know what the viral cause is. -Describe the structure of the infecting agent. -Does this type of infection indicate a co-infection?

The family Parvoviridae includes very small viruses (18-26 nm in diameter) that have naked icosahedral protein capsids with a single-stranded DNA genome. Maybe. There are two distinct groups within the Parvoviridae. One requires help by a co- infecting virus (usually adenovirus) to grow. The other group can replicate autonomously without the help of other viruses within the cell.

As a part of an effort to develop a universal influenza vaccine, you are tasked with the mission to discover highly conserved epitopes of the orthomyxovirus glycoproteins. What are the most common glycoproteins of this viral family and their function?

The hemagglutinin (HA or H) glycoprotein is the viral attachment protein. This binding initiates fusion of the viral envelope with the cellular membrane, thus permitting the virus to enter the cell. The neuraminidase (NA or N) glycoprotein cleaves sialic acid from glycoproteins (including HA) and glycolipid. This may serve to prevent virus from binding to itself and also promote virus release from the infected cell.

While trying to complete your graduate school thesis on ciliated epithelia, your cell lines keep getting infected with viruses. The viruses create multi-nucleated giant cells, and lead to eventual apoptosis. Basic PCR is unable to replicate the virus, but the addition of a reverse transcriptase allows for analysis. Describe the viral family, general pathogenesis, and transmission of the infecting agent.

The paramyxoviruses include the most important agents of respiratory infections of infants and growing children. Measles virus and measles are still prevalent in the developing world. All members of the paramyxoviridae family initiate infection via the respiratory tract.

Franklin D. Roosevelt was confined to a wheel chair due to the effects of a viral infection. Since it's always nice to connect your science knowledge with the humanities, explain the way in which FDR was paralyzed, from initial infection on.

The path of entry into the body for the Polioviruses is the mouth (fecal-oral transmission) and primary viral replication occurs in the oropharynx and intestine. A viremia carries the virus throughout the body and to other target tissues eventually leading to a viral infection of the central nervous system. Infiltration of the anterior horn of the spinal cord causes flaccid paralysis.

As a member of a CDC investigative team, you are called in to investigate a "swinger's club" in New York City. At this club, a variety of different individuals convene several times a week to have unprotected homosexual and heterosexual relations. Many of the members of the club are complaining of burning upon urination, and gram negative diplococci which ferment glucose are grown from their samples. Utilizing disease mapping, you discover the source of the infection. Upon testing this individual you discover that he has also just began to develop the classic symptoms of PML. Due to this, you order RT-PCR of his samples and a flow cytometry of his blood. His CD4 count is extremely low. You now begin to test the other members of the club with p24 assays. Nearly everyone comes back with positive results, expect a brother and sister (ewww) who frequent the club together. You do a further analysis of their genome, and discover that they contain a mutated gene for CCR5. -How does this allow them to be immune from the infection?

The primary target cell for HIV infection is the CD4+ helper T-cell and the major receptor is the CD4 protein found on the cell surface. The β-chemokine receptor 5 (CCR5) is the major co-receptor on CD4+ cells for macrophage-tropic HIV-1. The T cell tropic HIV-1 isolates use fusin (CXCR4) as a co-receptor. The viral attachment protein is the viral encoded glycoprotein (gp120) which interacts with the CD4 receptor protein.

Your free urban clinic begins to notice a high incidence of newly diagnosed HIV positive individuals with a rare form of splenic periarteriolar lymphoma. It appears as though the cancer develops within a year of contracting the virus. -What viral mechanism explains this phenomenon?

The retroviruses that quickly cause tumors have been found to have genes that are responsible for tumor induction. These genes are referred to as viral oncogenes. Oncogenes are genes, when over-expressed or when mutated, have the ability to transform a normal cell into a tumor cell. When oncogenes are functioning correctly within a normal cell, they are referred to as proto-oncogenes. The proto-oncogenes code for growth factors, growth factor receptors, signal transducers and transcription factors. Occasionally, a retrovirus can pick up a cellular gene by recombination and, in the process, it becomes a viral gene (the HIV virus in this vignette has picked up a gene that induces splenic neoplasm). When a retrovirus picks up a cellular proto-oncogene (c-onc) and in this process converts it to a viral gene (v-onc), then the proto-oncogene becomes oncogenic.

As a UN infectious disease expert, you are called-in to analyze a sample that was taken from a facility in Russia. The agent is determined to be a filamentous, enveloped, (-)ssRNA virus. Describe the pathogenicity of this virus.

There are four genetically different subtypes of Ebola virus. It appears that each subtype has a different level of virulence within humans. Ebola virus envelope glycoprotein, and the interaction of other viral proteins with the immune system plays an important role in the extreme virulence of this virus. Direct destruction of endothelial cells probably plays a primary role in hemorrhage.

While doing research into Picornaviruses, you accidentally forget to label your viral samples. In one tube you have placed relatively harmless strains of Rhinovirus, and in another tube you have placed extremely virulent, poliomyelitis-causing strains of Polio. -What bench-top test could you perform in order to discover which virus is which?

There are now three genus groups that are in the picornavirus family: Enterovirus, Rhinovirus, Hepatovirus (Hepatitis A Virus). Enteroviruses and Hepatitis A Virus are acid-stable, whereas Rhinoviruses are acid-labile.

An immunology researcher brings his son to you and demands that you give him the oral (Sabin) polio vaccine. You ask him why, and he tells you that he wants his son to have secretory IgA protection from the poliovirus. Although this logic is sound, you disagree with the decision. Why?

There are two types of poliovirus vaccines...an inactivated virus vaccine (Salk) and an attenuated live virus vaccine (Sabin). Each vaccine contains three poliovirus serotypes. In order to reduce the risk of vaccine-associated paralytic polio (caused by revertant mutants), it is now required that only inactivated polio vaccine be given in the United States (2000).

A village in Africa has an outbreak of hemorrhagic fever. Within 48 hours, 90% of the population is dead. What is unique about the survivors' immune responses? How was it transmitted?

There is no significant difference in viral antigen levels between survivors and non-survivors of the Ebola virus infection. Survivors have an increased IgM response and sustained, perhaps regulated, T cell cytokine responses. Temporary highly increased levels of inflammatory cytokines are found in non- survivor cases. Filoviruses are considered to be zoonotic (transmitted from animals) with the animal reservoir currently though to be fruit bats. The infected bats do not appear to suffer disease when infected.

A mother brings in her six year old girl to see you. She had serious vomiting followed by eight days of profuse diarrhea. Bacterial culture narrows down the diagnosis to a viral cause. -A virus from what family is the most likely culprit. How does disease occur? How did the girl contract the disease?

Three genera of Reoviridae can infect vertebrate animals: orthoreoviruses, rotaviruses and orbiviruses. Rotaviruses infect epithelial cells of the small intestine, replicate to very high numbers and are the most common cause of infantile diarrhea in the world. Rotaviruses are shed in large quantity in feces, can be water-borne and transmitted by fecal-oral routes. Nosocomial infections are quite common.

Part of your research deals with the insertion of GFP (green fluorescent protein) genes within viral genomes. Over the past week, you have been inserting GFP genes within the genetic codes of negative sense ssRNA viruses. Upon imaging analysis, you are surprised to see that one of the viruses causes a high level of intranuclear fluorescence. When you load the infected cells with mCherry (a red fluorescent protein) labeled guanine, you notice that the viral mRNA fluoresces. What virus are you studying, and what characteristics does the fluorescent analysis illustrate?

Transcription of influenza occurs in the nucleus. Post-transcriptional modification of viral mRNA includes the stealing of 5' caps from cellular mRNA's.

Your little brother has recently come down with a classical case of Chicken Pox. It is also very close to Thanksgiving, and the majority of your family is expected to come over tomorrow for a family party. Upon reflection, you remember being told previously that your 95 year old grandmother had never been infected with Varicella Zoster as a child. Given her age, she also never received the Varicella vaccine. You immediately tell your family that they must keep Grandma away from your brother. Why is this?

VZV infection of adults is usually more severe than of children. Symptoms can include life threatening pneumonia.

What are the trigger words of Calici viruses?

Viral gastroenteritis Norovirus

What are the trigger words for Rhinovirus?

common cold polyprotein protease

What are the trigger words for the Herpes Virus Family?

enveloped DNA large

What are the triggers words for the family Papillomaviridae?

genotype genital warts condyloma high risk integrated viral DNA oncogenes Papanicolaou smear Koilocytes viral like particles HPV vaccine squamous intra- epithelial lesion cervical cancer HPV

What are the trigger words for filoviruses?

hemorrhagic fever cytokines disseminated intra- vascular coagulation zoonotic disease reservoir encephalitis

What are some trigger words for CMV?

large owl-eye inclusion body swollen (megalo) cells opportunistic disease mononucleosis congenital intracerebral calcifications microcephaly

What are the trigger words for Paramyxoviruses?

measles morbilliform maculopapular rash croup syncytia negative sense RNA 3 C's Koplik's spots parotitis mumps RSV

What are some trigger words for EBV?

mononucleosis heterophile antibody monospot atypical lymphocytes ampicillin-induced rash immortalization

What are the trigger words for Coxsackievirus?

myocarditis pleurodynia hemorrhagic conjunctivitis herpangina

What are the trigger words for HSV?

neurotropic Cowdry Type A inclusion bodies syncytia Tzanck Smear recurrence vesicles

What are the trigger words for VZV?

neurotropic syncytia All stages of lesions present vesicles shingles chicken pox

What are the trigger words for Poliovirus?

poliomyelitis asymmetric flaccid paralysis Salk vaccine Sabin vaccine

What are the trigger words for Rhabdoviruses?

rabies Negri bodies prophylaxis hydrophobia incubation period vaccine

What are some trigger words for retroviruses?

retrovirus lentivirus provirus reverse transcriptase long terminal repeat (LTR) gag pol env integration oncogene diploid HTLV-1 adult T-cell leukemia tropical spastic paraparesis

What are some trigger words for HHV6?

roseola rash high fever

What are the trigger words for hepatitis?

serum hepatitis HBs Ag Australia antigen hepatocellular carcinoma jaundice icteric liver transplant partially double-stranded DNA parenterally HBIG chronic hepatitis (Hep-C)

What are the trigger words for poxviruses

variola vaccinia brick shaped molluscum contagiosum biological warfare recombinant vaccine monkeypox zoonosis

What are the trigger words for the bunyaviruses and arena viruses?

viral encephalitis arthropod vector transovarial trans- mission hemorrhagic fever hantavirus pulmonary syndrome rodent vector zoonosis

A 40 year old male presents to you with invasive hepatacellular carcinoma and portal hypertension. He soon develops esophageal varices, and expires. Serum analysis notes the presence of IgG HBcAb but no HBeAg. Was the patient infectious before he passed? What caused the cancer?

-Absence of HBeAg proves he was not infectious. -The HBV genome can integrate into host chromatin, and chronic infection correlates with the onset of primary hepatocellular carcinoma 20-30 years later.

You are on your surgical rotation. The previous morning, you assisted in the renal transplantation of a 17 year old male. Now, 24 hours after the surgery, he is exhibiting classical symptoms of graft rejection. Following normal protocol, his surgical team increases the dose of his immunosuppressive medication. Ten hours later, his condition has worsened, and he begins to exhibit signs of endocarditis. His O2 sat plummets, and he begins to become delirious. Suspicious of a secondary cause of rejection, you request an examination of his urine sample, and pathology alerts you of the presence of decoy cells. What is the most likely culprit of this patient's graft rejection?

-BK polyomavirus reactivated within a transplanted kidney can give rise to polyomavirus allograft nephropathy. This may lead to kidney transplant failure. The symptoms are often worsened by the use of immunosuppressive drugs following transplant -Decoy cells are virally infected epithelial cells that can be found in the urine, and are diagnostic for BK viral infection.

As a mad scientist, you are trying to develop a weaponized form of Coxsackievirus. In order to do this, you order samples of the two major strains from Taiwan. Unfortunately, the two vials come to you unlabeled, and you have no idea which one contains Coxsackievirus A and which one contains Coxsackievirus B. In order to sort out this speed bump, you deicide to infect some unsuspecting citizens and make your determination by the resulting symptamology. -What symptoms would indicate infection with which strain?

-Coxsackievirus A causes skin infections (herpangina: hand food and mouth disease) and eye infections (conjunctivitis). -Coxsackie B group viruses are associated with acute inflammation of the heart and other muscles.

As a part of an away rotation you take a trip to India. While there, you work at a local missionary health outpost. It is located far away from the nearest city, in a swampy area. Three days after your arrival, you develop a headache, rash, and severe back and bone pain 6-7 days. Describe the structure of the responsible agent.

-Dengue Fever, a Flavivirus -The Flaviviridae have an icosahedral protein capsid surrounded by a membrane envelope and one envelope glycoprotein. The genome is single-stranded, linear RNA having positive-sense. All members of the single genus flaviviruses are arthropod-borne.

What are the trigger words for Reoviruses?

-Double stranded RNA -Infantile diarrhea -Rotavirus -Rehydration

As a part of your graduate student thesis you are required to do observatory research on the cell cycle dynamics of differentiated keratinocytes. In order to do this, you are required to perform genetics assays on several genes that are only expressed during cell-growth. This presents a problem, because differentiated keratinocytes are no longer dividing. You consult one of your medical student friends (who is currently taking I&I) about this problem, and he suggests a viral solution. What viral proteins would be involved in this solution? By what mechanism, and why, does the virus do this?

-E6 and E7 Although HPV infects the basal keratinocyte, the virus requires a differentiated cell for complete viral replication. The viral genome contains genes that express proteins that interact with cellular control proteins to stimulate differentiated cells to activate DNA replication polymerases. The viral proteins that interact with the cellular control proteins can be referred to as viral transformation proteins. Uncontrolled expression of these proteins and their continual interaction with the cellular tumor suppressor proteins (Rb protein and p53 protein) is a step toward viral carcinogenesis.

A 12 year old presents with extremely elevated ALT. He had recently undergone a blood transfusion. You suspect an infectious cause. However, analysis is negative for HBV and HAV. -How do you know the cause is viral? What is the cause?

-Elevated ALT is specific for viral hepatitis Hepatitis C, a flavivirus, is associated with blood transfusion and drug use and is now the leading reason for liver transplantation in the U.S. Hepatitis C accounts for 20% of all cases of acute hepatitis.

A 23-year-old kidney transplant recipient exhibits symptoms of lymphoma. Immunosuppressive therapy is reduced. The lymphoma 'spontaneously' disappears. -What is the most likely culprit?

-Epstein Barr Virus

-A 15-year-old boy complains of being bone weary for the last 3 wks. He kissed his first girl 2 months earlier. -He has a sore throat, swollen glands and a fever. Upon examination, you note splenomegaly. Lab tests show atypical lymphocytes. Serum causes agglutination of sheep rbc, but not guinea pig rbc (Paul Bunnell test), and the presence of IgM to MA, VCA, and IgG to EA, but not EBNA. -What is the most likely culprit? -When will EBNA show up positive?

-Epstein Barr Virus -After recovery

On a mission trip to Honduras, you encounter a pregnant twenty year old female with joint pain. Upon physical examination, you notice a lace-like rash on her upper chest and the side of her neck. She states to you that two months ago she had been diagnosed with malaria. You become concerned. -How is the infecting agent causing joint pain in your patient? -Why are you concerned about the fact that this woman is pregnant? -What would have protected your patient from infection?

-Erythema infectiosum and a viral-associated joint arthritis are likely to be immune-mediated conditions in B19 virus infection. -B19 has been shown to cross the placenta and may be associated with fetal death. This is known as hydrops fetalis which is caused by abnormal accumulation of serous fluid in the fetal tissues. -Antibody against B19 appears to be lifelong and is protective against reinfection.

As a new researcher in an immunology lab, you are assigned to a project which is working on designing a new peptide-based vaccine. The vaccine platform utilizes an immuno-active peptide termed "J" (a portion of the Beta-2-Microglobulin portion of MHC I) which is linked via a triglycine linker to a desired antigen. In this way, the vaccine platform can be differentially designed in order to prime the immune response against different forms of infection. Your principle investigator asks you to design a vaccine prototype against Herpes Simplex Virus. -Which envelope glycoprotein which aids in HSV viral attachment would be a good antigenic target to link to J?

-Glycoprotein D. -gD binds directly to HVEM, a member of the tumor necrosis factor receptor superfamily and a mediator of HSV entry.

As a researcher of HSV, you routinely work with a strain of herpes simplex in your lab. One day, you discover that the strain was isolated from a child who died from encephalitic HSV. -What are the normal and severe types of HSV infection?

-HSV usually causes benign, but troublesome recurrent oral and genital infections. -The most serious HSV infections cause encephalitis, recurrent keratoconjunctivitis, leading to blindness, and neonatal HSV. -HSV infections of the neonate, newborn or immunocompromised individual can disseminate and be life-threatening.

A ten year old female presents to you with a large, classical wart on her thumb. You treat it with liquid nitrogen and an oral antiviral. What caused the wart in your patient? Describe its pathological process.

-Human papillomaviruses (HPV) infect keratinocytes of the squamous epithelia at many sites of the body and can be divided into a group that infects cutaneous skin and those that infect mucosal skin. -Those that infect mucosal skin can be further divided into a high risk association with cervical cancer and low risk viral genotypes.

A four year old female presents to you with acute meningitis. Broad spectrum IVAB treatment is initiated, and she recovers three days later. An analysis of her CSF indicate the presence of naked positive sense RNA viruses. -What was the most likely cause of illness?

-Infection by Echovirus--MOST COMMON CAUSE OF VIRAL ASEPTIC MENINGITIS -Coxsackie and echoviruses are picornaviruses which may cause central nervous system infection, often infecting meninges, but are usually benign.

While on your OB/GYN rotation, you help deliver a baby who is born with severe congenital defects. Despite heroic intervention, the patient expires. You follow the patient's samples to the pathology lab, and a section of the child's liver shows multiple basophilic inclusion bodies. -What was the cause of the child's congenital defects?

-It has been estimated that one in every 10,000 infants born in the USA is seriously retarded or hearing impaired as a result of a congenitally-acquired CMV infection. -Fetal infection with CMV can result in small size, microcephaly, intracerebral calcification, jaundice, rash, and hepatosplenomegaly.

You administer a vaccine to one of your pediatrics patients with consists of VP4 and VP7. Hopefully, this will protect the child from one of the most common viral infections in children of the US. -Describe the genome and structure of the virus.

-It's the vaccine for the Rotavirus The Reoviridae are medium-sized viruses having a double protein capsid shell and containing 10-12 double-stranded RNA molecules as the genome. Each RNA segment contains a separate viral gene.

You are assigned to do research on a novel herpes simplex drug called Nanoviricide (TM). The drug consists of nano particles which have been embedded with multiple viral attachment receptors which bind to the glycoproteins of HSV. In theory, HSV viruses should bind their envelopes to the drug and prematurely initiate the attachment process of infection--causing the uncoating of the virus in the extracellular space and subsequent inactivation. In order to test the efficacy of the drug, you design a plaque assay. In order to do this, you treat several VERO cell lines (a monolayer of African Green Monkey Kidney Cells) with the drug, and then infect them with encephalitic strains of HSV-2. After leaving cell lines in tissue culture for 48 hours, you view them using phase contrast microscopy. -The absence of what structure in the cell line would indicate efficacy of Nanoviricide (TM)?

-Many strains of HSV and VZV can cause cell-cell fusion (syncytia). -The absence of synctia would indicate efficacy

You decide to counter Dr. Rosenthal's TEM identification (HSV V.S. EBV) challenge by changing the analysis technique to gel capillary electrophoresis. You bet that you can distinguish between HSV and EBV by looking at their differential migration on an agarose gel. Should he take you up on the bet?

-No -Although they are all double stranded linear DNA, the length and complexity of the genomes of HSV, VZV, EBV, CMV and HHV-6 are different. Therefore, a gel could be used to distinguish them

You are invited to the grand opening of NEOMED's brand new Transmission Electron Microscope. At the grand opening, Dr. Rosenthal bets your $1000 that you can't use the device to distinguish between his samples of HSV and EBV. Should you take him up on the bet?

-No -EBV, CMV and HHV-6 are morphologically indistinguishable from HSV and VZV.

While on a cruise to Barbados you become sick with severe gastroenteritis. In order to prevent the spread, you are whisked away by members of the crew and quarantined within a small padded room for the duration of the cruise. During your misery, you keep yourself sane by reviewing medical concepts in your head. While reflecting on your sickness, you come up with an idea of what the infectious agent is. Describe its genome and structure.

-Norovirus -Caliciviruses have a small, naked, icosahedral protein capsid containing single- stranded, positive-sense RNA as the genome.

You are called in to treat a pair of sexual partners who are presenting with completely different disease symptoms. The woman is a 27 year old female, who is presenting with multiple genital warts and pelvic pain. A cervical exam and biopsy confirm the diagnosis of invasive cervical caner. The male is 54 years old, and an avid intravenous drug abuser. He has scabes and esophageal-invasive thrush. You order an HIV test which comes back positive. He is currently developing severe mental disturbances--and you suspect a cause other than HIV. Viruses from what two families are infecting these individuals? Describe their structure and genome.

-Papillomavirus/Polyomavirus -Specifically HPV (female) and JK (male) -These two virus families contain viruses that have a naked icosahedral protein capsid (45 - 55 nm in diameter) and a double-stranded circular DNA genome. They use to be one family known as the Papovaviridae.

One of your classmates takes a trip to Ecuador. When he comes back, he developed diffuse muscle pains and malaise. That is soon followed by the appearance of macules, then papules, and vesicles (all in the same phase) which cover his body and the velar surfaces of his hands and feet. The student makes a complete recovery with minimal supportive treatment Describe the replication cycle of the infecting virus.

-Patient has monkeypox Monkeypox is a zoonosis infection that resembles smallpox but is less severe in its presentation. Even though poxviruses are DNA viruses, the entire replication cycle occurs in the cytoplasm of the infected cell. There is an ordered morphogenic process that involves a proteolytic cascade for poxvirus maturation and infectivity. The viral proteinases involved are highly conserved and may be future antiviral targets.

As an infectious disease expert at the UN, you are called in to investigate a small town in Syria which was allegedly the target of biological warfare. Donning your hazmat suit, you enter the town with an army of investigators in order to examine the infected and dying. The patients you encounter are covered with macules and papules, all of which are in the same phase (not in crops). The mortality rate is high. Describe the structure and genome of the infecting agent. How does this virus overcome the requirements of mRNA processing?

-Patient has smallpox Poxviruses are very large and complex enveloped DNA viruses. The family contains genera such as the orthopoxviruses and molluscipox that infect humans. The genome is ds linear DNA, containing approximately 200 genes. The virion contains enzymes, including a transcriptional system, that can synthesize, polyadenylate, cap, and methylate viral mRNA.

A seven year old girl is brought into your pediatrician's practice with the classic symptoms of the common cold. Rapid strep antigen comes back negative, and due to lack of tonsilar inflammation, you are fairly certain that the overnight culture will prove negative as well. You do not prescribe antibiotics to the girl, as you believe the cause to be viral. The mother gets angry at this, as she wants you to give her daughter antibiotics since they will "make her better." -Explain to the mother the most likely causative agent of the girl's symptoms, and its structure. -How can this girl be reinfected after this first infection?

-Picornaviruses are very small viruses (25-30 nm in diameter) that have an icosahedral protein capsid surrounding a single-stranded, linear positive-sense RNA genome. -Rhinoviruses are isolated from the nose and throat and cause upper respiratory tract infections including the common cold. -Natural immunity to the rhinoviruses develops but may be brief as resistance to the virus appears to depend on secretory antibodies (IgA).

While studying in the NEOMED library, you come across the Iron Lung machine which is located in the corner by RDEC. While contemplating the impact of infectious diseases on the US populace, a BioMed student comes up from behind you. He asks you what the iron lung was used for. -Explain to the BioMed student (in the cocky way that only a medical student can accomplish) the reason why Iron Lungs were used--including the epidemiology and classification of the infecting agent.

-Poliovirus is a member of the Enterovirus group and is the cause of a severe paralytic disease called poliomyelitis. However, most Poliovirus infections are subclinical. -Poliovirus invades specific nerve cells associated with motor muscle control and, in the process of replication, may destroy many of these cells. Infection of the brain stem with Poliovirus may lead to loss of breathing control--requiring an iron lung for forced respiration.

A 65 year old man had severe headaches, tremor of the hand, and was forgetful and confused. His condition deteriorated and he entered a coma with occasional clonic twitching. On autopsy, there was intracellular vacuolation seen throughout the cerebral cortex. Diagnose him.

-Prion disease (Spongiform encephalopathy)--Probably CJD

While rotating through OB/GYN, you deliver a baby who is suffering from cardiac septal defects and cataracts. When taking a history from the mother, you discover that she was never vaccinated as a child. Describe the structure of the responsible agent.

-Rubella--A Togavirus -The Togaviridae have an icosahedral protein capsid surrounded by a membrane envelope and two envelope glycoproteins. The genome is single-stranded, linear RNA having positive-sense. One genus, the alphaviruses, is arthropod-borne; other groups, including rubiviruses (rubella), are not carried by vectors, but are directly infectious human-to-human via respiratory route.

While at the drug store this September you notice that several customers are receiving intranasal vaccinations. All of the customers are from the ages 20-40. The customers who are over 60 are receiving intramuscular injections. -What serotypes are virus are contained in these vaccinations? Describe their structure and viral family. What is unique about their genomes?

-Serotypes A and B -The orthomyxoviruses (Influenza virus types A, B and C) have a lipid envelope protein coat and segmented, (-) RNA genomes. -The 8 segments of the viral genome for A & B serve to encode 10 different proteins.

As a member of the CDC's infection task force, you are on the way back from investigating a Bordatella Pertussis outbreak in Seattle. While you are waiting at Akron Canton airport to make your connection into Heartsfield-Jackson in Atlanta, you realize that one of your fellow passengers has several vesicles on his face. They are surrounded by patches of red, and some of them are crusting over. Next, you realize that his four year old son is covered in macules, papules, and vesicles that present in crops. Several of the passengers of the plane are elderly, and you are worried that the recirculation of the air during flight will promote spread of one of their infections. -Which individual would be most likely to cause respiratory spread? -Which individual would vaccinated persons be protected from? -What serotype is the father infected with?

-The child has Varicella Zoster and the father has an HSV outbreak. -HSV is transmitted by contact, whereas VZV is mainly spread by the respiratory route, but also by contact. -HSV-1 and HSV-2 can infect the same sites; but HSV-1 is usually associated mechanisms of action with infections above the belt and HSV-2, below the belt. -There is a live attenuated vaccine available for VZV, but there is no vaccine available for HSV.

An eight year old female is brought to your office with a six day history of "pink eye" and sore throat. You run a rapid strep test which comes back negative. -Describe the structure and replication of the infecting agent.

-The family Adenoviridae includes viruses (70-90 nm in diameter) that have a naked icosahedral protein capsid, projecting protein fiber and a linear double- stranded DNA genome. -The gene transcription pattern of adenoviruses is very complex with introns and overlapping genes present within the viral genome. -The adenovirus replication cycle is divided into an early phase and late phase which occur in the nucleus of the infected host cell. During the viral growth cycle, synthesis of host cell macromolecules is inhibited, leading to cell degeneration.

While on an away rotation to the US/Mexico border, you encounter two patients with similar symptoms. One of the patients complains of headache, rash, and pain that makes it feel as if his "bones are cracking open." Your other patient presents with fever, headache, muscle weakness, nausea, and vomiting. This turns into a coma. MRI indicates no specific location of lesions. His family tells you that he lives next to a wetland. -Which patient could transmit his infection to you?

-The former patient has Dengue Fever, and the latter has West Nile Virus. Humans may be part of the viral life cycle such as in yellow fever virus and dengue virus or may be incidental hosts that may not permit the virus to build up in amount to be further carried to new hosts (dead-end hosts). Examples of arboviruses in the USA involved with humans as dead-end hosts are Eastern equine and Western equine encephalitis viruses, St. Louis encephalitis virus and, most recently, West Nile virus.

You are rounding at a college health center. A 21 year old female comes to you, distressed, because she just discovered that her roommate has HSV-II genital herpes. She is worried that she may catch the virus, since she shares the same toilet as her roommate. What structural characteristic of the herpes virus can allow you to reassure your patient that this will not happen?

-The herpes viruses are large enveloped DNA viruses. -Enveloped viruses are less likely to be transmitted via fomite

One of your AIDS patients begins to present with severe mental distress. You perform PCR on a draw of CSF fluid, and the PCR is positive for an organism which has a double-stranded circular DNA genome. What was the route of initial infection? What is the mechanism of neuro-involvement?

-The human polyomavirus site of entry may be the respiratory tract followed by a viremia and deposit into the kidney. A number of conditions may reactivate latent virus such as immunosuppressive chemotherapy, pregnancy, immunodeficiency disease, and kidney transplantation -JC virus, a human polyomavirus, is the cause of a rare demyelinating disease of the central nervous system called progressive multifocal leukoencephalopathy (PML). -JC virus, a human polyomavirus, is the cause of a rare demyelinating disease of the central nervous system called progressive multifocal leukoencephalopathy (PML). -PML appears to be due to the direct action and destruction of oligodendrocytes by JC virus.

A 23 year old homeless female presents to you with an esophageal C. albicans infiltration. She reports that she has been using IV drugs since the age of 11. Flow cytometry shows normal fluorescence of cells labeled with FITC-anti-CD8, but no fluorescence of cells labeled with tomato-anti-CD4. -Describe the replication of the infecting agent.

-The life cycle of the retroviruses may be divided into two distinct phases: (1) early phase - entry, reverse transcription of viral RNA into DNA insertion of DNA into the host genome; (2) late phase - expression of viral RNA's and proteins, the assembly of virion particles, release of virions by budding through the plasma membrane. Reverse transcriptase makes a double-stranded DNA copy of the genomic RNA and this DNA copy integrates into the cellular genome. The integrated viral DNA is called a provirus and serves as the template for viral mRNA and genomic RNA. The viral genes are flanked by long terminal repeats (LTR) that control viral gene expression. The retroviruses encode at least 3 genes (gag, pol, env) which are translated into polyproteins. These genes are essential for viral reproduction.

While on a mission trip in Africa you treat a patient with fever, coagulopathy, petechiae, liver and spleen necrosis, and visceral hemorrhage with no CNS involvement. The members of his village tell you that he is a shaman, and lives with a large number of animals. You suspect an arboviral cause, however, several of the people who have had direct contact with him develop symptoms as well. -Describe the infecting agent. What is its usual host?

-The man has Lassa Fever--caused by an Arenavirus The major host for arenaviruses is small rodents in which the virus usually establishes a persistent infection. Arenaviruses endemic to South America (Junin Virus, Machupo Virus) and Africa (Lassa Fever Virus) can cause a severe and fatal hemorrhagic fever. These viruses infect humans via aerosols. Lassa Fever Virus, an arenavirus of Africa, can be passed by human-to-human contact.

A 17 year old African American male presents to you with severe abdominal pain and hepatomegaly. He had originally gone to the ER, and now he is in the intensive care unit. The ER said that he was negative for both HbsAg and HbsAb. They were unsure what his diagnosis was, and ordered a CT scan which confirmed hepatomegaly but noted nothing else of importance. You decide to hold a white piece of paper up to his eyes, and notice that they are visibly tinted yellow. You order a second serum draw, and notice the presence of HbcAb. -Why did the ER miss this diagnosis? What serum antibodies would indicate infection resolution? Which ones would indicate infectivity? Where do they come from?

-The patient has HBV, but he is in the window period. Due to this, his HbsAg and HbsAb are all in immune complexes, and are undetectable by assay. During HBV replication an abundance of HBsAg is produced and secreted into the blood. HBsAg can be detected in saliva, nasopharyngeal washings, semen, menstrual fluid, vaginal secretions and blood. Detection of antibody to HBsAg in the absence of HBsAg correlates with resolution of infection. During acute HBV disease, presence of HBeAg in the blood correlates with the presence of infectious virus. HBcAg and HBeAg are found in the virus capsid while HBsAg is found in the envelope. Antibody to HBsAg elicits protective immunity.

After months of petitions, you convince NEOMED to let you take an away rotation to Guatemala. In the country you are assigned to a small village with limited medical care. One day, you see two separate patients with nearly identical symptoms. The first patient is a five year old male with extremely swollen tonsils and supraclavicular lymph nodes. There is a serous exudate from his oropharynx, and he has a fever of 104 degrees farenheit. His family is healthy, and his symptoms began several days prior. The second patient is a sixteen year old girl. She presents with the same tonsilar and pharynx-based symptoms as your first patient, but in addition to lypmphoidopathy she also presents with splenomegaly. Your town has limited phlebotomy capacity, and you must be very sensitive to how many tests you order on each patient. -In which patient would you be most likely to detect a positive antibody for Paul Bunnell antigen? What is a possible cause of the other patient's symptoms?

-The teenage girl would most likely be positive. EBV infection of children is relatively benign, but the highest incidence of EBV-induced infectious mononucleosis is in teens and young adults. The virus is transmitted in saliva (e.g. kissing). -The child could possibly have Diptheria. Do a Schick test to confirm.

An IV drug user presents to your ER with a low CD4 count and abdominal pain. He swears to you that he has been vaccinated with the HBV vaccine, but that he has never had HBV in the past. Serum analysis shows high levels of HBsAb and HBcAb. Why do you know that your patient is lying?

-The vaccine available for HBV is HBsAg produced by a recombinant DNA in yeast cells or mammalian cells. -The vaccine would not elicit an HbcAb response--only active infection would do that.

On your recent trip to China, you visit a hospital which has been swamped with cases of nasopharyngeal carcinoma. The locals of the town believe that the government is doing secret experiments on them in order to test biological weapons (which isn't that unrealistic, honestly), however, you suspect a different cause. You take samples from several patients and head to Hong Kong, and upon examination with a TEM, you detect viral infiltrates in their tumors. -Describe the structure and genome of the virus which was detected.

-The virus is EBV -It is a large, enveloped icosahedron with a double stranded linear DNA genome

A 42 year old man presents with high fever, headache, vomiting, and backache after travel in Central America. Later he experiences bleeding gums, blood in urine, blood in vomit, petechiae, and jaundice. -What is unique about all of the viruses in the infecting agent's family? Describe the characteristics in detail.

-They are all Arboviruses. Arboviruses are defined as viruses that replicate in an arthropod and are transmitted by bite to a vertebrate host. The invertebrate host is considered to be the vector and the vertebrate host is called the reservoir. Most arbovirus infections are limited to a primary viremia causing mild flu-like symptoms; but serious disease may result from infection of secondary target tissues such as vascular epithelium, liver or brain.

Two days after you take the Virology I and I exam, you notice extreme stabbing pain in your T4 dermatome. The pain is isolated to the left side, and is also accompanied by parasthesia. At first, you are worried that your recent diet of Monster, Pizza, and 5 Hour Energy (in preparation for the exam) has begun to catch up to you. However, upon listening to your heart sounds, everything appears normal. Once you look in a mirror, you realize that a rash is developing around the area that your pain is occurring. -What is the most likely culprit?

-VZV recurrence (zoster/shingles) occurs upon reduction of immune control (>50 years of age) and affects an entire dermatome. -The primary VZV infection is Varicella or Chickenpox, and the recurrent VZV infection is zoster or shingles.

A 16 year old girl presents to your office complaining of a three day history of fever, malaise, headache, and sore throat. She is unwilling to talk about her condition with you, until you suggest that her mother should step out of the room. Two days prior, vesicles began to appear on the back of her throat and they subsequently ruptured to form ulcerative lesions with grayish exudates on the tonsils and the posterior pharynx. Upon questioning you discover that she has a 21 year-old boyfriend who goes to a nearby university. Her mother is unaware of the relationship. Recently, they have become sexually active, but your patient claims that they haven't "gone all the way." -How would you confirm your diagnosis?

-Your patient is suffering from an HSV-2 infection which was transmitted via orogenital contact -Laboratory diagnosis of HSV is by isolation and growth in tissue culture, cytopathology, antigen detection or genome detection (e.g. PCR) -The lab would look for Cowdry Type A inclusion bodies, syncytia, and Tzanck cells

A six year boy is in your office because of pink eye. He was sent home from school because one eye was found to be blood red. Now both eyes are red. There has been watery discharge but no pus. His eyes are painful to him. He has had a mild sore throat, persistent cough and slight fever. What is most likely the cause of the infection? How did the child get the infection? Would you prescribe antibiotics? Will the infection spread to other parts or tissues of the boys body? Do you need to know if there are any underlying conditions? Do others in the house need to be fearful of getting the infection? What laboratory assistance do you need in making the diagnosis?

1. Adenovirus 2. Respiratory or from fomites 3. No, it is viral 4. It can be respiratory or GI, but it normally does not spread past the lymph nodes 5. Immunocompromised can have more complications 6. Yes 7. Rule out strep (rapid test), diagnose by PCR and hemataglutinin

As you are rotating through pediatrics, a father brings in his two children to see the physician. One of the children is 3 months old, and the other is six years old. They both have different types of symptoms. First of all, the three month old is suffering from severe watery diarrhea. It began three days ago, and has been getting worse ever since. A day after the onset of his brother's illness, the six year old began to develop watery eyes and swollen tonsils. During their physical exam, you notice that their father's right eye is red. You ask him about the symptamology, and he states that he has had "pink eye" for the past week. -How was this infecting agent spread between the family? -How did it evade the immune system? -Why do the different family members have different symptoms? -Is there a vaccine?

1. Adenoviruses are spread mainly through respiratory and fecal-oral routes. 2. Adenoviruses can block expression of major histocompatibility complex (MHC) class I proteins by suppressing their gene expression and also inhibiting protein transport to the cell surface 3. There are a great number of diseases associated with the adenoviruses and these include: acute respiratory disease, pharyngitis, pharyngoconjunctival fever (in children), epidemic keratoconjunctivitis (in adults), infant diarrhea, pneumonia, acute hemorrhagic cystitis. 4. A live, non-attenuated vaccine against specific types 4 and 7 has been developed and is used in military recruits. Antibody should be lifelong against a specific type.

Mr. I., a 26-year-old native of England who had lived in Florida for 14 years, sought medical attention in November 2005 for depression and memory loss that was interfering with his work performance. He was referred to a psychologist for his complaints. However, in December he developed involuntary muscle movement, difficultly walking and dressing, and incontinence. In January 2006 he went to a local emergency room where a computerized tomography scan of the brain was found to be normal, and he was treated for an anxiety attack. Later that month, at his mother's urging, Mr. I. returned to the family home in England. By then his symptoms had worsened: he experienced falls and could not shower or dress himself; he could not recall his phone number or do simple arithmetic. An evaluation for variant Creutzfeldt-Jakob disease (CJD) was conducted: an EEG was normal, and MRI of the brain showed high signal intensity in the pulvinar and thalamus bilaterally. Subsequently, a tonsil biopsy was performed. Tonsillar tissue was examined by immunoblotting and immunohistochemical staining for the protease-resistant form of prion protein (PrPSc). Both were positive and consistent with variant CJD. Sequencing of the patient's PRNP alleles showed homozygosity for methionine at position 129 but no mutations. Mr. I. had no history of transfusions, transplants, or major surgery. In spite of an attempt at experimental therapy with quinacrine, the patient's decline continued. By September 2006 he was bedridden and unable to eat or communicate. 1. What features of Mr. I.'s case are characteristic of variant CJD? 2. How and when did he acquire the disease? 3. Should he be isolated to prevent transmission of the disease to others? 4. What are his chances for recovery?

1. At the age of 26 years, he is very young for any of the other human prion diseases. The onset with psychiatric symptoms is very typical of vCJD and distinct from the onset of sporadic Creutzfeldt-Jakob disease (CJD). His evaluation included magnetic resonance imaging that showed high signal intensity in the pulvinar, which is characteristic of vCJD. In addition, a tonsillar biopsy was positive for PrPSc, a finding that does not occur in other human prion diseases. Finally, he has the PrP codon 129 homozygosity for methionine, indicating that he belongs among the 30% of humans susceptible to variant CJD. 2. Mr. I. likely acquired variant CJD by ingesting beef or beef products containing the BSE PrPSc. Although it is not clear when this might have occurred, it is unlikely that he acquired variant CJD in the United States. He moved to Florida in 1992, and it is possible that he was previously exposed in Great Britain, when the BSE outbreak there was in full swing. 3. No. He should not be placed in isolation because only certain of his tissues contain prions (central nervous system, lymphatics). Person-to-person transmission of variant CJD does not occur with normal contact. However, if he had a brain or tonsillar biopsy, one would assume that the instruments had become contaminated. They would likely be discarded after that use rather than used in a subsequent surgery on another patient, because contaminated surgical instruments could be a vehicle of transmission with prion diseases. 4. Unfortunately, Mr. I. will not survive.

A ten year old girl is brought to the office (USA) at the start of what appears to be a bright red rash on the face. About 10 days earlier she had a fever, chills, headache and myalgia. Vital signs are currently normal. No sore throat is reported and a rapid group A streptococcal antigen test is negative. What virus is the likely cause? Where does this virus replicate? What other potentially serious and life threatening diseases are associated with this virus? ◦ Under what underlying conditions in your patient would these diseases occur?

1. B19 Virus (Parvovirus) 2. In the nucleus 3. Aplastic Crisis, Hydrops Fetalis 4. Anemia

As a concierge physician, you are called in to treat Robert Downey Jr. on the set of Iron Man 4. According to your patient, he has been feeling extremely tired as of late, despite his use of copious amounts of caffeine and "uppers." Upon physical exam you note extreme hepatomegaly and splenomegaly. He is also beginning to develop a sore throat and a cough. Mr. Downey Jr. is worried that he is developing cancer, but you reassure him that there could be any number of different causes. He admits to you that he sleeps with several "call girls" every week, but that they all get "tested monthly." A biopsy of his central lymph code shows the presence of extremely abnormal T cells. When you apply his serum to a blood assay, it coagulates sheep and bovine erythrocytes but fails to coagulate gerbil erythrocytes. -What specific type of disease does Robert Downey Jr. have? -What name is given to the abnormal cells in his lymph nodes?

1. EBV is the cause of heterophile-positive infectious mononucleosis and has also been strongly associated with Burkitt's Lymphoma, nasopharyngeal carcinoma, and other neoplasias. 2. Clinical diagnosis is based on Symptoms (fatigue, fever and the TRIAD: Lymphadenopathy, Splenomegaly, Exudative Pharyngitis); CBC (blood counts); laboratory detection of heterophile antibody (antibody directed against the Paul Bunnell antigen on sheep or bovine erythrocytes), serology for viral antigens, or PCR. 3. EBV infected B cells trigger a large T cell response which is seen as atypical lymphocytes (Downey Cells) and causes swollen lymph nodes and spleen.

An outbreak of a severe hemorrhagic fever occurs in a village within south central Africa It appears that bats are the animal reservoir Clinical features include profuse bleeding in the eyes and gastrointestinal tract Secondary infection rates were highest among those caring for the sick Mortality rate was greater than 70% What virus was the cause of this outbreak? Could you distinguish this virus from others such as Yellow fever virus, Dengue virus or Lassa virus?

1. Ebola virus--a Filovirus 2. You can distinguish them by the high mortality. In addition, Yellow Fever and Dengue are Flaviviruses, whereas Lassa is an Arenavirus.

A 30-year-old woman comes to the office for a gynecologic exam. There are no medical complaints at this time. You notice that her last exam was 5 years ago. She smokes is divorced and sexually active with a younger man. Her previous Pap smears have all been normal. The one you took comes back with the conclusion of High Grade Squamous Intraepithelial Lesion (HGSIL). An immediate biopsy is recommended. What is the most likely viral cause of the woman's condition? What is the hallmark of infection of this virus at an earlier stage of disease? Where would you find the viral genome in the patient's cells?

1. HPV 2. Koilocytes (enlarged, wrinkled nuclei, large cytoplasmic halo) 3. Within the nucleus

One of your fellow medical students begins to complain of sensations of burning pain, itching, hyperesthesia (oversensitivity), and paresthesia ("pins and needles": tingling, pricking, or numbness) exclusively on the left side of his neck. Recently he has also been experiencing quick stabs of agonizing pain. A small vesicular rash is visible, with a slight serous exudate. It's the week before the I&I final. -What is the cause of your classmate's pain? -Why are the symptoms occurring now?

1. HSV and VZV establish latent infection of neurons. The pain is caused by reactivated VZV (herpes zoster) 2. It's the week of finals. Stress can trigger HSV and VZV recurrences. Immune suppression can trigger HSV and VZV recurrences.

While rounding you encounter an AIDS patient who is suffering from CMV. Your attending begins to grill you on the intricacies of herpes viruses. Sadly (and much to the disappointment of your I&I colleagues) you come up short on the information. After a thorough scolding, you go home, determined to educate yourself on herpes. -What are the phases of herpes virus replication? -What types of infection can herpes viruses cause? -What type of immunity is most important in combatting herpes? -For what subtypes of virus are antivirals available? -Where is herpes found?

1. Herpes virus protein synthesis occurs in three phases: immediate-early, early and late. 2. All human herpes viruses can cause lytic, persistent and latent infections depending on the target cell type. 3. Cell mediated immunity is very important for the control of herpes viruses. 4. Antiviral drugs are available for HSV, VZV, and CMV. 5. The herpes viruses are ubiquitous.

Your patients are young boys suffering from a severe immunodeficiency called X linked severe combined immunodeficiency (XSCID). They have the most common genetic form that affects a single gene. You are attempting to replace the defective gene with a functioning gene using a retrovirus. The outcome was such that the immune defect was cured but the boys came down with leukemia. The trial was halted until further study could be carried out. The virus vector was shown to be the cause of the leukemia even though the vector is a defective retrovirus. Knowing the life cycle of retroviruses what is a possible event that must be examined as the cause of the leukemia? Previous animal studies greatly underestimated the risk of this event from occurring in humans.

1. Insertional Mutagenesis

A 25-year-old man died of AIDS due to treatment failure. He suffered from a loss of speech, vision and coordination which was originally thought due to AIDS related dementia. However, a brain biopsy detected foci of demyelination in the brain with a depressed number of oligodendrocytes. What virus would be typically considered as the cause of the neurodegeneration? What is the disease called? How does the virus cause this disease? Had you been able to diagnose and note the symptoms what therapeutic approach might you have added to the patients' HIV therapy?

1. JC virus 2. PML 3. JC lytic infection of oligodendrocytes. Demyleinating 4. Anti-retrovirals, Cidofovir (Nucleic Acid analogue), Topoisomerase inhibitors

A 4-year-old boy in Ohio was taken to the ER in mid- September when he complained about a stiff neck and pain in his head. Earlier in the day he a brief seizure after which a persistent headache continued. CT scan, CSF was negative for pathogens. A 10 day course of acyclovir was prescribed. Eventually the boy recovered with little to no obvious sequelae. Serology and titer of acute and convalescent blood samples confirmed the cause as viral and the results were reported to the state health department. The boy's back yard is filled with trees and squirrels. What is the most likely cause of the boy's infection? What are other causes that make this case complicated in the medical world? What environmental factors are important in thinking about this case? Why the great effort to provide an accurate diagnosis for this case?

1. La Crosse Virus (a Bunyavirus) 2. Could easily be confused with rabies, herpes encephalitis, mumps, bacterial, mycoplasmal, protozoal, mycotic infections 3. La Crosse virus happens in the later summer (this case is in September), the virus tends to replicate in squirrels, and be transmitted by mosquitoes. 4. In order to prevent incorrect anti-biotic or anti-viral (acyclovir) treatment, unnecessary brain biopsy, and prepare for future neurologic sequelae

You enter a contest to win $1 billion by developing a cure for the common cold. One of your rivals in trying to develop a selective inhibitor to the virus's attachment receptor, but you decide to develop a drug that interferes with viral replication. In order to do this, you develop an inhibitor that can enter mucoid epithelia cells using the properties of hydrophobic nano particles as a vehicle. Your inhibitor does not target ribosomes or RNA-dependent-RNA polymerases. -What receptor is your rival's drug targeting? -What necessary component of replication is your drug targeting?

1. Members of the immunoglobulin superfamily and related molecules are receptors for picornaviruses. The presence of specific receptors determines the host cell specificity for a particular virus. 2. The positive-sense genome of Picornaviruses encode a polyprotein that must be proteolytically cleaved to produce enzymatic and structural proteins. One of the first proteins cleaved off acts as an RNA dependent RNA polymerase which aids in viral genome replication. If the drug is not targeting a polymerase or the translating ribosome, the proteases that cleave the polyprotein is a good target.

A 17 year old female presents to you with pain upon urination. From the urine sample you isolate gram negative diplococci which ferment glucose but fail to ferment maltose. Based upon this evidence, you decide to treat your patient with Azithromycin, since it is active against a common co-infection. However, knowing the statistics of STI transmission and being a concerned physician, you also decide to order a Pap smear of your patient. One of your medical students questions this decision, due to the absence of condyloma acuminata. What was your patient's original infection? What co-infection does Azithromycin treat? How do you justify the extra test to your medical student? What hallmark sign would indicate a positive result on the test?

1. Neisseria gonorrhea 2. Chlamydia trachomatis 3. HPV infection of the genital tract is sexually transmitted, warts being an obvious clinical lesion of infection. Condyloma lesions from HPV may also be flat and not readily observable. 4. Cytologic analysis of cervical smears (Papanicolaou Smear) will sometimes show koilocytes which indicate viral infection.

A young male patient of 21 years is brought to the office by friends in Kent, OH. He has had a night of severe vomiting followed by a profuse watery diarrhea and abdominal pain. He claims he was not drinking last night. There are several other young college age adults in the waiting room. One common component to their history was that they had eaten a local restaurant known for good, inexpensive food. -Can you make a guess as to the virus causing such an infection? -What factors indicate that it is not the virus for this case? -How long will the patient be sick? -What treatment is available? How long will they shed the virus? -Can they be attacked again? -What other bacterial species should you consider for this case?

1. Noravirus 2. All ate at the same restaurant 3. 24-48 hours 4. 2 weeks viral shedding 5. They may be able to be infected again. Different strains/immunity is lost 6. Staph aureus, B. cereus

A ten year old African American male presents to you with severe exhaustion. He is a special needs patient, and was born with a tracheoesophageal fistula. Due to this, he has undergone several reconstructive surgeries, and he takes his nutrition via a G-tube. His mother has been having difficulties feeding him, and she believes that a different gauge tube is necessary for her son now that he is growing. At birth he was diagnosed with sickle cell disease. Upon physical examination, you do not notice anything unusual except for extreme exhaustion and frequent yawning. You order a blood draw, and severe anemia is diagnosed. Bone marrow biopsy confirms an extremely low reticulocyte number. -What disease of what infectious agent is your patient suffering from? -What hallmark diagnostic sign is lacking from his presentation, and why? -How does this agent replicate, and how is it spread

1. Parvovirus B19 is the cause of a serious illness known as aplastic crisis which occurs in patients having a chronic hemolytic anemia and subsequent viral infection. 2. The human parvovirus B19 is the cause of fifth disease (erythema infectiosum), a childhood rash clinically known as slapped cheeks because of its appearance. The rash is difficult to notice due to the fact that he is African American. 3. Parvoviruses only replicate in actively dividing cells. Parvoviruses are transmitted by the upper respiratory route and then spread to the blood system especially infecting erythroid precursor cells.

On October 14, a 26 year old man developed vomiting and bloody diarrhea with a 2 day history of chest discomfort, numbness and tremors of the left arm. At the hospital he was treated with anti- emetic suppositories; later that evening he became disoriented, combative, and had difficulty breathing. Broad spectrum antibiotics and acyclovir were started. On the 20th the patient developed cardiac arrhythmia, hypotension, and required sedative therapy to induce paralysis. Five days later he developed respiratory failure and died. The house occupied by the patient was found to contain a colony of 200 silver haired bats in the attic with further openings from the attic to the bedroom. -What is the most likely cause? -What antemortem samples and exam should be conducted in this case? -What would be found in the samples? -What could have been done to prevent the symptoms?

1. Rabies from bat bite--A Rhabdovirus 2. Brain biopsy 3. Negri bodies 4. Injection of human Rabies IgG at the bite site, and a Rabies vaccine as treatment.

An 18-year-old male patient presents to the clinic in December. He previously (3 days ago) had an acute onset of high fever (40C), headache, tiredness and dry cough. He is still very sick today with the same symptoms. His pulse is normal. His eyes appear normal. Would you bother to do a rapid test and what would it test for? What would you expect from a nasopharyngeal sample culture? What antipyretic would you prescribe? Why should this be a concern? Would anti-viral drug therapy be of use at this point in time? What differential are you attempting to assess in this case?

1. Rapid strep 2. Normal flora 3. Ibuprofen. Do not prescribe aspirin, because it may cause Reye's Syndrome (usually only in infants) 4. No, it must be used during prodrome. 5. Strep

A 70-year-old Mexican man presents to the hospital emergency room (USA) after a sudden loss (flaccid paralysis) in the use of his right leg. His son reports that he previously had several days of headache, fever and a sore throat. All of his other limbs are functioning and have normal sensation. The father is on a visit from Mexico to family living in the USA. The son reported that a recent vaccine day was advertised whereby all the children in his father's home village in Mexico including some of his grandchildren were given an oral vaccine via a sugar cube. What is the most likely infectious cause of the flaccid paralysis? Why does the paralysis develop? What other infections, viral and bacterial, could be part of the differential diagnosis? What is a potential source of the infection?

1. Reverted Poliovirus from oral vaccine 2. Viremia spreads to anterior horn motor neurons 3. Clostridium botulinum 4. Oral Vaccine

An infant has Infant has rapid breathing, low grade fever, and bronchiolitis. He is two and a half months old. -Why did this infection occur at this age? -How should you treat him?

1. Severe respiratory syncytial virus disease begins to occur in infants at two to four months of age, when maternal antibody levels are decreasing. 2. Severe cases of respiratory syncytial virus infection of infants are treated with ribavirin administered as an aerosol.

Last year, I became ill with severe gastroenteritis following the second MTC module exam. For the first two days I experienced a generalized sense of malaise, and nausea of unknown origin. By Thursday I felt very ill, and was barely able to drag myself to Sarah's apartment for her to take care of me. First, I had extremely watery diarrhea, followed by several episodes of intense vomiting. Later that night I had a high fever with rigors. Sarah did an excellent job of aiding in my recovery, but by Sunday she was ill with the exact same symptoms. -What was the most likely cause of my infection? How long afterwards did I shed virus? Can I be infected again this year?

1. The Norwalk virus group is now known as Noroviruses genus of the Caliciviridae family, and they are the cause of a substantial number of acute gastroenteritis cases. 2. Both water and food-borne transmission of Norwalk Virus can occur, and epidemic conditions have been found with school children, adults and family contacts. Viral shedding occurs for at least two weeks after infection. 3. Immunity to Norwalk Virus is brief and does not resemble the general pattern for most viruses. Adults may slowly acquire immunity upon repeated infection.

One of your pediatric patient's mother calls your office. She states that her family is on vacation in Europe, and that her 7 year old son has developed a rash. Without being about to see your patient, it is difficult to diagnose him. However, she states that the child's rash began on his face and spread downward. Your patient never received the MMR or Varivax. -Via the description of the rash's progression, what does your patient have? What other childhood rashes could it be, and how do they spread?

1. The rash is due to rubella. German measles rash starts on face and SPREADS DOWNWARDS over the trunk and extremities. The facial rash usually clears up as it spreads over the rest of the body. 2. It could also be measles (rubeola). Rubeola rash starts on the back of the ears and, after a few hours, SPREADS to the head and neck before spreading to cover most of the body, often causing itching. 3. It could also be chicken pox. Varicella zoster rash begins ON THE TRUNK, and then spreads peripherally out to cover the extremities.

A 60-year-old man from Cuyahoga Falls, OH was brought to the hospital suffering from an acute flaccid paralysis of the left leg. He retains all sensation in his limbs. He had previously suffered a febrile illness of fever, headache, backache, myalgia and anorexia for 5 days. Electromyography studies ruled out Guillain- Barre syndrome. The patient is an avid walker in the early evening hours. Serologic tests results are ongoing. What is the likely infectious cause of the clinical presentation? Notice that there are non-infectious diseases that have similar symptoms. How is the agent transmitted and how did your patient get the infection? How does the agent cause the symptoms? What is the outcome that may be expected with the patient? What would the serologic laboratory tests for levels of IgM or IgG show? Do you need to worry that you may contract the infectious agent?

1. West Nile Virus based encephalitis 2. From birds via Culex mosquitoes to humans 3. Causes acute encephalitis, especially in those with heart disease/elderly 4. He will probably survive 5. IgM will persist for several months after infection. 6. No, WNV is a dead end in humans--cannot go from human to human, even with the proper vector.

While traveling in Asia you see several patients who are on artificial respiration via ventilators. A hospital attending tells you that they have Severe Acute Respiratory Syndrome. -What is the cause of their infection?

A novel coronavirus, SARS-CoV, has been identified as the causative agent for the deadly severe acute respiratory syndrome (SARS). This virus and disease have disappeared from the world so-far.

One of your patients comes down with an extremely severe case of influenza. As a precaution, you place the patient's family members on prophylactic amantadine. Despite the early intervention, the patients still develop influenza. What does this tell you about the infecting virus's serotype?

Amantadine and rimantadine inhibit uncoating of the virus and have been used to provide protection against type A influenza when given within 24 hours of infection. The use of these antiviral drugs has been limited by their side effects on the central nervous system and by their ineffectiveness against B influenza. There are very exciting new antiviral drugs that inhibit neuraminidase that have been found to be highly effective against both A and B influenza viruses.

A patient presents to you with severe jaundice and abdominal pain. Serum analysis indicates very high HbsAg and no detectable HbsAb. The infection resolves itself very quickly (although it had been extremely severe), and later on he is found to have no levels of HbcAb or HbeAg. What part of this patient's adaptive immunity is responsible for the response to infection?

An active cell-mediated immune response to HBV causes liver cell damage and correlates with more pronounced symptoms and resolution of the infection, whereas mild disease usually correlates with subsequent chronic infection.

A proposed prion disease drug aims to actively bind and opsonize amyloid plaques for microglial digestion. What secondary protein structure should be targeted by this drug?

Beta pleated sheets--A major hallmark of prions.

A fifteen year old male presents to you with extremely swollen tonsils and splenomegaly. He admits to you that he kissed his first girl three months prior. A titer of the patient's blood is negative for VCA, EA, and MA. EBNA is also negative. You decide to biopsy the patient's lymph nodes, but you do not detect the presence of abnormal T cells. The patient's serum is unable to agglutinate cow erthyrocytes. -At first glance, what appeared to be the viral cause of symptoms? What is the true cause?

CMV is the most common, opportunistic viral disease of AIDS patients. EBV causes heterophile-positive mononucleosis, while CMV causes heterophile- negative mononucleosis.

How would you confirm HIV diagnosis in a patient?

Detection of antibody against HIV by enzyme immunoassay and Western blot is used to indicate infection. Western blot assay results must reveal antibodies against specific viral protein combinations in order to be considered definitive.

A 3 month old infant is rushed into your ER with a 105 degree fever. His mother is in hysterics, and the child is nearly non-response. After treatment with paracetamol, the child's fever rapidly dissipates, and a rash appears on the child's face. -What is the most likely cause of disease?

HHV-6 is the causative agent of roseola (i.e. exanthem subitum), a common disease of childhood characterized by high fever and the appearance of a rash coincident with a drop in fever.

As a director at the CDC, you begin to receive disturbing reports of an HIV virus that has been mutated such that it is able to infect any cell which expresses CCR5, and not just CD4/CCR5 cells. -A major mutation in what gene most likely allowed for this new ability?

HIV, within any individual, steadily changes over time. Virus variation occurs most in the env gene. The changes are mainly due to the error-prone reverse transcriptase and virus replication.

A 3-year-old exhibits vesicular and ulcerative lesions around the mouth approximately 4 days after being visited by Grandma. The vesicles look like "dewdrops on a rose petal." They break and crust over. The child has a mild fever and swollen glands. Symptoms lasted 2 weeks. Grandma had a single vesicular lesion at the "crimson border of the lip." Four days prior to her visit, Grandma was skiing in Vail. -What is the most likely culprit?

HSV-1

A 23-year-old, sexually-active woman complained of fever, dysuria, swollen glands and ulcerative vesicular sores on the cervix, vulva and vagina for approximately 5 days. Her symptoms recur on a monthly basis. Prophylactic antiviral drug therapy is prescribed. -What is the most likely culprit?

HSV-2

A patient of yours has just been diagnosed with an early stage melanoma. In the past, he has had HSV outbreaks in the same area as the melanoma. Now that his cancer has developed, he has been undergoing a persistent active infection in the area. He questions you as to why this is? -What factor of a herpes virus would cause this phenomenon?

Host cell control (regulation) of transcriptional expression of viral genes is the major determinant of the outcome of infection.

You are a physician who works KSU's health center. After winter break a 19 year old freshman female presents to you complaining of extremely painful sores on her feet. Upon questioning, you discover that your patient never wears shoes or socks when she's in her dorm room--including when she walks in the common areas. You diagnose the patient's sores as plantar warts. After warming up to you some, the patient also reveals that she is suffering from a more personal problem--and upon examination you diagnose condyloma acuminata. What serotypes of what virus are causing your patient's symptoms? Based upon these diagnoses, what other serotypes would you be worried that your patient is infected with?

Individual HPV types cause specific lesions: HPV 1 and 4 in plantar warts, HPV 6 and 11 in anogenital warts (condyloma acuminata) and laryngeal papillomas, HPV 16 and 18 in carcinoma of the cervix.

Individuals who have been infected with the H5N1 avian flu tend to expire due to massive cytokine storms. These storms consist primary of acute phase cytokines, and lead to increased vascular permeability and septic shock. Why does this occur?

Infection of respiratory epithelial cells results in many cells being infected and cell death. Interferon is released and may be involved in host recovery. Antibodies to HA and NA are important in immunity. Cell-mediated immunity is involved in viral clearance as cytotoxic T cells lyse infected cells. -If the strain is extremely virulent, spikes in interferon and TLR activation lead to cytokine storms and death due to inflammation.

What are the prion-based diseases that affect humans?

Kuru, Creutzfeldt-Jakob Disease (CJD), Gerstmann-Sträussler-Scheinker Syndrome (GSS), fatal familial insomnia (FFI), and two emerging diseases, namely new variant CJD (vCJD) and sporadic fatal insomnia (sFI).

As a part of your OB/GYN rotation, you assist in delivering a baby from a 19 year old prostitute. The infant is born premature, and is confined to the NICU. Several days after partuition, you are ordered by your attending to check on the infant's status. Although none of the NICU nurses have taken notice, the child appears to be in respiratory distress. Upon listening to the child's respiratory sounds, you notice a high-pitched stridor. Following normal procedures, the NICU staff increases the concentration of the child's exosurf regimen (a synthetic pulmonary surfactant). Despite this effort, the child's status worsens. Scared for your patient, you begin to think critically. You take samples from the patient's mother, and although the pathology comes back normal, a genetic assay comes back positive for a naked DNA virus. What is the cause of the child's respiratory distress? How was it transmitted?

Laryngeal papillomavirus transmission probably occurs during birth in the course of fetal passage through an infected birth canal.

An international sporting event was held in central Pennsylvania. Baseball teams from Japan, Canada, and Mexico were present. One 12-year-boy on the Japanese team had a sore throat and malaise when arriving to the hotel. Several days later he had a rash, cough, Koplik's spots, fever (102.4F) and coryza. Only one other young boy became infected with this virus. When does the infectious period of this virus extend from before rash to days after rash onset? What is the virus's attack rate? What does the small number of cases in this epidemic suggest?

Measles 1. 5 days before to 4 days after 2. This virus has the highest attack rate known (greater than 90% in the non- immune). 3. The small number of cases in this outbreak shows the value in maintaining high vaccination coverage and also suggests the importance of the continual promotion of control in other countries.

A 29 year old man presents to your reproductive clinic, and tests indicate that he is sterile. He explains that when he was younger he had a viral infection that gave him bilateral orchitis. What other symptoms does this virus usually cause? What family does this virus come from?

Mumps virus infection commonly includes the parotids and may involve several other tissues and sites. Paramyxovirus.

While at Cuyahoga county's Greek Festival you notice that the old man running the roast lamb booth has a granulomatas lesion on his right hand. At first glance it looks similar to a B. anthracis infection, but the man tells you that the lesion appeared after he cut his hand on a sharp lamb's bone. What is the cause of infection?

Orf virus is a zoonosis of sheep, goats, or cows that can infect humans by direct contact.

You are a pediatrics doctor. One of your patient's comes in with severe bronchiolitis. Two patient's later you see one with a barking seal cough. Which virus would cause a more severe disease if transferred to the patient's parent?

Parainfluenza can cause serious disease in children and adults, RSV can cause serious disease in children but a mild infection of adults.

What are the trigger words for Coronavirus?

SARS

A 33 year old man presents to a clinic in Africa with initial flu-like symptoms. He soon complains of vomiting and blood and bloody diarrhea. He dies the next day. Describe the family and structure of the infecting agent.

The Filoviruses have a pleomorphic shape often filamentous in form. The virions contain a linear single strand negative-sense RNA genome. These viruses are enveloped and carry a viral glycoprotein that is important for vascular cell injury.

42-year-old male presents with two large non-pruritic, painless, vesicular lesions on thumb and fore finger; he denies any other symptoms. He works in a farm and recently purchased juvenile goats at auction, some of which had ulcers on their oral mucosa.

The Orf Virus. • Infection appear as painless ulcerative or vesicular skin lesions, commonly occur on fingers, after occupational contact with infected animal or contaminated fomites.

A 12 year old female presents to you with plantar warts which she acquired during her trip to summer camp. Looking at her vaccination history, you strongly suggest that she receives what vaccination which covers what serotypes of virus from the same family?

The quadrivalent (types 6, 11, 16, and 18) HPV vaccine (Gardasil; Merck) has FDA and European commission approval for use in women between the ages of 9-26.

A 14 year old female presents to you with some of the worst condyloma acuminata you have ever seen. Upon questioning, the female swears to you that she is not sexually active. Despite this, she has been a competitive swimmer since childhood. You accept the fact that her papillomavirus infection could have been caused by fomite interaction, however, you wonder how such a small viral load could have resulted in such a horrible infection. Being an intelligent physician, you order a head and neck film. The film reveals the absence of a thymus, and your patient is diagnosed with DiGeorge Syndrome. Why does this diagnosis explain your patient's symptoms?

The role of the immune system in viral clearance is not known in molecular detail. However, there is evidence to suggest that cellular-mediated immunity is important in the control of viral infection.

A girl in your community is bitten by a bat. At the hospital they give her a prophylactic vaccine. Describe the treatment that was given. How is it created?

There are several rabies virus vaccines. One is grown in human diploid fibroblast cells and is inactivated before given to patients who have been bitten by a suspected rabid animal. The vaccine is also given as a preventive measure to people who come into close contact with animals that may encounter other rabid animals.

A 12-year-old boy has a fever and complains of itching blister-like lesions on his body. You observe vesicles, pustules, and dried, scabbed lesions. -What is the most likely culprit?

VZV

A 28-year-old pediatric resident has fever, pneumonia and 3 days later develops a disseminated maculopapular rash -What is the most likely culprit?

VZV

A 65-year-old woman has sharp pain and itching in right ear, numbness and tingling in right side of face. Vesicular rash and severe pain followed. Pain continued after rash resolved. -What is the most likely culprit?

VZV

23-year-old male medical student presents with diffuse pustular skin lesions (on upper and lower extremities, including volar surfaces), lymphadenopathy, fever, headache, and backache. He recently returned from Democratic Republic of Congo, where he examined patients with undiagnosed febrile illness with skin lesions who had contact with rodents. What is the most likely culprit?

• Rash similar to smallpox, appear commonly on volar surfaces of extremities • Person to person spread and mortality are lower than smallpox • The reservoir of virus remains unknown, likely to be rodents