Micro Lab 4

Retroviruses

(+) Retrovirus RNA genome is converted into DNA, which is integrated into the host chromatin and transcribed as a cellular gene

Envelope

A membrane composed of lipids, proteins, and glycoproteins

capsid

A rigid structure able to withstand harsh environmental conditions

vesicular lesions

Blister that likely contains viruses (shingles/chicken pox)

Dengue virus

Break-bone fever High fever, headache, rash, and bone pain that lasts for 6-7 days. Rechallange with a different strain can result in dengue shock syndrome (DSS). See previous explanation under flaviviruses

Chikungunya virus

Crippling arthritis associated with infection of this virus. This will be the next major disease to hit the US as the A. aegypti mosquito vector spreads

resolution

Decrease in severity of the symptoms

Variola

Disease: smallpox Source: humans Location: extinct

HHV6

Herpes lymphotropic virus

properties of a virus

NONLIVING Filterable agents Reproduce by assembly of the individual components; must self-assemble (rather than by binary fission like bacteria) Genome consists of DNA or RNA, but NOT BOTH; packaged in a protective shell of protein and, for some viruses, a membrane Lack the capacity to make energy, substrates, or their own proteins Cannot replicate their genome independently of the host cell must be adapted to the biochemical rules of the cell in order to use cell's biosynthetic machinery Naked capsid or an envelope morphology Must be infectious to endure in nature Must encode any required processes not provided by the cell

most common sites of viral infection and disease

Oropharynx and respiratory infection Pharynx Tonsils Bronchi Lungs

Quarantine

a state, period, or place of isolation in which people or animals that have arrived from elsewhere or been exposed to infectious or contagious disease are placed Previously the only way to stop/ contain epidemics Example- small pox

positive-strand RNA viral genomes

act as mRNA, bind to ribosomes, and direct protein synthesis i. The naked positive-strand RNA viral genome is sufficient to initiate infection by itself ii. After the virus-encoded, RNA-dependent RNA polymerase is produced, a negative-strand RNA template (antigenome) is synthesized iii. The template can then be used to generate more mRNA and to replicate the genome

Vector

animal/ insect which serves as a route of transfer for viral disease into other animals and humans or other locales

Enveloped Viruses

i. NOT as durable- fragile 1. Require an intact envelope for infectivity ii. Must be wet 1. Treatment with acid and detergents- this prevents them from being transmitted by fecal-oral route iii. Transmission 1. Respiratory droplet, blood, mucus, saliva, semen 2. Injections 3. Organ transplants i. ***Exceptions are HBV and coronaviruses

The incubation period for CJD and kuru

may be as long as 30 years, but once the symptoms become evident, disease progresses rapidly, and death usually occurs within a year

Epidemic

occurs over a large geographical area Usually from a new strain of virus introduced into an immunologically naïve population Example- ebola epidemic in west Africa

HSV - 1

primary target: Muco-ep cells site of latency: trigeminal ganglia means of spread: direct usually orally clinical disease: gingivostomatitis, kertoconjuctivitis, pharyngitis, encephalitis (can cause genital herpes too) recurrent disease: cold sores lab diagnosis: Both (cowdry type A acidophilic intranuclear inclusion bodies; syncytia; tzank smear multinucleated giant cells) Vacc: No Cancer: No

Papillomavirus

stimulates cell growth and DNA synthesis

Poxviruses include

variola (smallpox- category A agent!), molluscum; think zoonosis

Pandemic

worldwide epidemic Usual resulting from the intro of a new virus (e.g. HIV) Pandemic of influenza A used to occur approx. every 10 years as the result of the intro of new strains of the virus

risk population of RSV

· Who Is at Risk? · Infants: lower respiratory tract infection (bronchiolitis and pneumonia) · Children: spectrum of disease mild to pneumonia · Adults: reinfection with milder symptoms

structure of the herpesviruses

· large, enveloped, icosadeltahedral capsids containing linear, double stranded DNA genomes · encode proteins and enzymes that facilitate replication and interaction of the virus with the host · in the tegument (space between envelope and capsid) are viral proteins and enzymes that help initiate replication outer viral glycoproteins

Hemagglutinin(HA)

• glycoprotein; binds sialic acids on epithelial cell membrane and promotes membrane fusion • Responsible for virus ENTERING cell o Causes agglutination of RBCs • Neutralizes Antibody response

Picornaviruses, Togaviruses, Flaviviruses, Caliciviruses, and Coronaviruses

(+) RNA genome resembles mRNA and is translated into a polyprotein, which is proteolyzed. A (−) RNA template is used for replication. For togaviruses, coronaviruses, and caliciviruses, early proteins are transcribed from the genome and late proteins from the template.

Picornaviruses, Togaviruses, Flaviviruses, Caliciviruses, and Coronaviruses

(+) RNA genome resembles mRNA and is translated into a polyprotein, which is proteolyzed. A (−) RNA template is used for replication. For togaviruses, coronaviruses, and caliciviruses, early proteins are translated from the genome and late proteins from smaller mRNAs transcribed from template.

Reoviruses

(+/−) Segmented RNA genome is a template for mRNA (+RNA). (+) RNA may also be encapsidated to generate the (+/−) RNA and then more mRNA.

Reoviruses

(+/−) Segmented RNA genome is a template for mRNA. (+) RNA may also be encapsulated to generate the (+/−) RNA and then more mRNA.

Transformation

(immortalization): viruses establish persistent infection and can cause uncontrolled growth continues without changes to morphology or metabolism Increase rate of sugar metabolism Loss cell contact inhibition mechanisms- continue to grow w/o senescence

Nonenveloped Viruses

(naked capsid viruses) viral capsid is surrounded by a bilayer membrane i. More hearty/ durable- can withstand drying, detergents, extreme pH and temp. ii. Can withstand the stomach pH and the detergent-like bile of the intestines and mild disinfection and insufficient sewage treatment iii. Transmitted by the respiratory and fecal-oral routes 1. Ex) hep A (picornavirus) is acquired from contaminated water, shellfish and food i. Sidenote: ii. Fomite- virus that is acquired from a contaminated object iii. Ex) contaminated handkerchief or toys

Orthomyxoviruses, Paramyxoviruses, Rhabdoviruses, Filoviruses, and Bunyaviruses

(−) RNA genome is a template for individual mRNAs, but full-length (+) RNA template is required for replication. Orthomyxoviruses replicate and transcribe in nucleus, and each segment of the genome encodes one mRNA and template

Orthomyxoviruses, Paramyxoviruses, Rhabdoviruses, Filoviruses, and Bunyaviruses

(−) RNA genome is a template for individual mRNAs, but full-length (+) RNA template is required for replication. Orthomyxoviruses replicate and transcribe in the nucleus, and each segment of the genome encodes one mRNA and is a template

unique properties of Paramyxoviruses

- Large virion consists of a negative-sense RNA genome in a helical nucleocapsid surrounded by an envelope containing a viral attachment protein (hemagglutinin-neuraminidase [HN] for parainfluenza virus and mumps virus; hemagglutinin [H] for measles virus; or glycoprotein [G] for respiratory syncytial virus [RSV]) and a fusion glycoprotein (F). -Virus replicates in the cytoplasm. -Virions penetrate the cell by fusion with the plasma membrane and exit by budding from the plasma membrane. -Viruses induce cell-to-cell fusion, causing multinucleated giant cells. -Paramyxoviridae are transmitted in respiratory droplets and initiate infection in the respiratory tract. -Cell-mediated immunity causes many of the symptoms but is essential for control of the infection.

inclusion bodies

- histological changes in cell due to virus or virus induced changes in cell structure **intranuclear basophilic (owl's eye) inclusion bodies: cytomegalovirus (CMV)- see on sediment from urine - Cowdry type A: found single cells or in large syncytia- HSV or VZV - Rabies = Negri bodies in the brain

the flu vaccine

-The influenza vaccine is a mixture of extracts or purified HA and NA proteins from three different strains of virus. The vaccines are prepared from virus grown in embryonated eggs and then chemically inactivated. -Ideally, the vaccine incorporates antigens of the A and B influenza strains that will be prevalent in the community during the upcoming winter -As of 2008, all children aged 5 to 18 years should also be vaccinated. Persons with allergies to eggs should not get the vaccine. -A live vaccine is also available for administration as a nasal spray instead of a "flu shot." The trivalent vaccine consists of reassortants for the HA and NA gene segments of the desired influenza strains.

Major differences between CJD and vCJD

-the age of occurrence and duration of illness - vCJD seen in younger people and they experience a longer

stages in viral infection in a host cell

1) Incubation 2) prodrome 3) acute phase 4) resolution 5) convalescence

Replication of picornaviruses: a simple (+) RNA virus

1, Interaction of the picornaviruses with receptors on the cell surface defines the target cell and weakens the capsid. 2, The genome is injected through the virion and across the cell membrane. 2′, Alternatively, the virion is endocytosed, and then the genome is released. 3, The genome is used as mRNA for protein synthesis. One large polyprotein is translated from the virion genome. 4, Then the polyprotein is proteolytically cleaved into individual proteins, including an RNA-dependent RNA polymerase. 5, The polymerase makes a (−) strand template from the genome and replicates the genome. A protein (VPg) is covalently attached to the 5′ end of the viral genome. 6, The structural proteins associate into the capsid structure, the genome is inserted, and the virions are released on cell lysis.

Replication of rhabdoviruses: a simple enveloped (−) RNA virus

1, Rhabdoviruses bind to the cell surface and are (2) endocytosed. The envelope fuses with the endosome vesicle membrane to deliver the nucleocapsid to the cytoplasm. The virion must carry a polymerase, which (3) produces five individual messenger RNAs (mRNAs) and a full-length (+) RNA template. 4, Proteins are translated from the mRNAs, including one glycoprotein (G) which is co-translationally glycosylated in the endoplasmic reticulum (ER), processed in the Golgi apparatus, and delivered to the cell membrane. 5, The genome is replicated from the (+) RNA template, and N, L, and NS proteins associate with the genome to form the nucleocapsid. 6, The matrix protein associates with the G protein-modified membrane, which is followed by assembly of the nucleocapsid. 7, The virus buds from the cell in a bullet-shaped virion.

pathogenesis of HPV including koilocytes, viral serotypes that cause cervical carcinoma, and viral proteins that act as oncogenes

1. HPV infect and replicate in squamous epithelium of skin and mucous membranes to induce proliferation. 2. Wart - cell growth/thickening of the basal prickle layers stratum spinosum 3. Koilocyte - characteristic of HPV. Cell growth/thickening in stratum granulosom.

A 50-year-old man was visiting family in Liberia and stayed in a house infested with rodents. He developed severe flu like symptoms, a sore throat, and red eyes and was treated with amoxicillin and chloroquine. His condition worsened with increased fever, severe headache, swollen lymph nodes, tonsils, and spleen. The patient started to cough up blood and then went into shock and then died. 1 How was this individual infected with Lassa fever virus? 2 What are the unique characteristics of arenaviruses? 3 How are they similar to bunyaviruses? Different?

1. Lassa fever is carried by small mammals, such as mice, and is transmitted by inhalation of aerosols, the consumption of contaminated food, or contact with fomites contaminated with mouse saliva, feces, or urine. 2. Arenaviruses have nonfunctional ribosomes in the virion, and the genome consists of two single-stranded ambisense RNAs. 3. Like arenaviruses, the bunyaviruses have multiple single-stranded ambisense RNAs that are surrounded by an envelope but without ribosomes. Hantaviruses are transmitted in mouse saliva, feces, and urine, but the other bunyaviruses are transmitted by arthropods. The Bunyaviridae and Arenaviridae share several similarities. The viruses of these families are negative-strand ribonucleic acid (RNA)-enveloped viruses with similar modes of replication. Both are zoonoses; most of the Bunyaviridae are arboviruses (ARthropod BOrne virus), but the Arenaviridae are not. Many of the viruses from these families cause encephalitis or hemorrhagic disease.

the type of vaccine for Yellow fever virus

17D live attenuated vaccine for yellow fever. It is the only approved human vaccine for any of the VHF's. However, there are experimental vaccines for all of the other ones, but you can't test their efficacy because it is not ethical to challenge human subjects with a VHF for which there is no cure

virion consists of

A nucleic acid genome packaged into a protein coat (capsid) or a membrane (envelope) The virion may also contain certain essential or accessory enzymes or other proteins to facilitate initial replication in the cell Capsid or nucleic acid-binding proteins may associate with the genome to form a nucleocapsid, which may be the same as the virion or surrounded by an envelope

Epidemic Keratoconjunctivitis

Adenoviruses cause a follicular conjunctivitis in which the mucosa of the palpebral conjunctiva becomes pebbled or nodular, and both conjunctivae (palpebral and bulbar) become inflamed. May occur sporadically or in outbreaks that can be traced to a common source (Ex: swimming pool conjunctivitis). Risk factors include irritation of the eye by a foreign body, dust, debris, and so forth May be an occupational hazard for industrial workers: more than 10,000 cases in people working in naval shipyards during 1941 and 1942. (Conjunctivitis caused by adenovirus)

Arboviruses (arthropod-borne)

Alphavirus (+ssRNA resembling mRNA with icosahedral capsid envelope takes the shape of the capsid. The capsid is made purely of protein C) Alphaviruses are cytopathic for vertebrate cells and shut off macromolecular synthesis. Their enzymatic proteins are translated first which helps promote rapid production of virions.

Viropexis

Alternate method of viral entry into host cells: Hydrophobic structures of capsid proteins may be exposed after viral binding to the cells, and these structures help the virus or the viral genome slip through (direct penetration) the membrane

alphaviruses (in the Togavirus family) and flavivirus transmission and unique features

Arboviruses (arthropod-borne) Sinbis Semliki Forest Eastern equine encephalitis Western equine encephalitis Chikungunya (transmitted by the Aedes mosquito) Has 2 replication phases. It first replicates nonstructural proteins and then the structural synthesis 1. Rubivirus a. Rubella (German measles) 2. Arterivirus ii. Flavivirus (+ssRNA, icosahedral capsid that is enveloped) 2. Antibodies to one flavivirus may neutralize the others because they have an E viral glycoprotein in common. You might think that is antibody production is a great thing, but it is not always. Flaviviruses get bound by nonneutralizing antibodies and then enter a cell with Fc receptors, usually a macrophage. This enhances the infectivity of the virus because it actually wants to be eaten by the macrophage. Dengue virus in particular can cause much more severe disease when challenged with another strain. 3. The major difference between flavivirus and alphavirus is that this time, the 5' end of the flavivirus genome has the structural genes. Since protein synthesis happens starting at the 5' end, structural proteins are first transcribed with more efficiency. This actually allows a lag before the production of new virions which delays the immune response. Another notable difference is flavivurses obtain their envelope by budding from the ER instead of the plasma membrane. The problem with this is the virus is then released by exocytosis or cell lysis. This is not efficient because our plasma membrane has a way of keeping the new virions associated with the plasma membrane so they can't get free. 1. West Nile Virus (transmitted by culex mosquito mostly in summer months) 2. Dengue 3. Yellow Fever (aedes mosquito) a. Inactivated viral vaccine 4. Japanese encephalitis a. There is an inactivated viral vaccine 5. St. Louis encephalitis (transmitted by culex mosquito) 6. Hepaciviridae (Hepatitis C)

clinical progression of measles and possible complications

CCC= cough coryza (runny/stuffy nose), conjunctivitis (early stage) fever can last 4 days and reach 104 degrees F rash starts on face and moves downward pneumonia is a complication. more seriously- objective #3 encephalitis (SSPE)

Yellow fever virus

Called yellow fever because the skin and whites of the eyes turn bright yellow from jaundice. Other symptoms are general. Fever, headache, vomiting.

Chronic Infection

Chronic hepatitis occurs in 5% to 10% of people with HBV infections, usually after mild or inapparent initial disease. Approximately one third of these people have chronic active hepatitis with continued destruction of the liver leading to scarring of the liver, cirrhosis, liver failure, or PHC. The other two thirds have chronic passive hepatitis and are less likely to have problems

type of vaccine used for measles virus

Composition: live attenuated viruses Measles: Schwartz or Moraten substrains of Edmonston B strain Mumps: Jeryl Lynn strain Rubella: RA/27-3 strain Vaccination schedule: at age 15 to 24 months and at age 4 to 6 years or before junior high school (12 years of age) Efficiency: 95% lifelong immunization with a single dose

Properties of DNA Viruses

DNA is not transient or labile. Many DNA viruses establish persistent infections (e.g., latent, immortalizing). DNA genomes reside in the nucleus (except for poxviruses). Viral DNA resembles host DNA for transcription and replication. Viral genes must interact with host transcriptional machinery (except for poxviruses). Viral gene transcription is temporally regulated. Early genes encode DNA-binding proteins and enzymes. Late genes encode structural and other proteins. DNA polymerases require a primer to replicate the viral genome. The larger DNA viruses encode means to promote efficient replication of their genome.

The genome of the virus consists either of

DNA or RNA i. The DNA can be single or double stranded, linear or circular ii. The RNA can be either positive sense (+) (like mRNA) or negative sense (−) (analogous to photographic negative), double stranded (+/−) or ambisense (containing + and − regions of RNA attached end to end) iii. The RNA genome may also be segmented into pieces, with each piece encoding one or more genes

Nonenveloped virus = naked capsid virus

DNA/RNA genome + structural proteins = nucleocapsid = naked capsid virus Sometimes may also contain enzymes & nucleic acid binding proteins to assist in attachment to host cell or initiate replication

vCJD (variant Creutzfeldt-Jakob disease)

Disease acquisition: -Ingestion of contaminated beef (most common) -injection -transplantation of contaminated tissue -contact with contaminated medical devices Clinical Symptoms Tend to present with psychiatric symptoms more in the beginning than CJD · visual deterioration and eventual blindness. · dementia. · involuntary muscle contractions. · muscle paralysis. · slurred speech. · difficulty swallowing. · incontinence. · coma.

Kuru

Disease acquisition: -initially limited to small area of New Guinea highlands related to cannibalism -women and children handled the food and ate less desirable viscera so developed kuru more often -neural tissue contains highest concentration of kuru agent Clinical symptoms: ● trouble walking ● increasingly poor coordination ● difficulty swallowing ● slurred speech ● moodiness ● muscle twitching and tremors ● pain in the legs and arms ● random laughing and/or crying No treatment

CJD (Creutzfeldt-Jakob disease)

Disease acquisition: -injection -transplantation of contaminated tissue -contact with contaminated medical devices Clinical Symptoms · visual deterioration and eventual blindness. · dementia. · involuntary muscle contractions. · muscle paralysis. · slurred speech. · difficulty swallowing. · incontinence. · coma. No treatment

Molluscum contagiosum

Disease: many skin lesions Source: humans Location: worldwide

Vaccinia

Disease: used for small pox vacc Source: lab product Location: N/A

Eastern equine encephalitis

EEEV can progress to encephalitis. Equine encephalitis viruses usually affect livestock more than humans but affected humans experience fever, headache, and decreased consciousness three to ten days after infection Generally resolves without sequelae but paralysis, mental disability, and seizures can occur

three potential outcomes of a viral infection

Failed infection (abortive infection) Cell death (lytic infection) Replication without cell death (persistent infection) Presence of virus without virus production but with potential for reactivation (latent-recurrent infection)

the flu-like symptoms generally associated with viral infections

Fever Malaise Anorexia (loss of appetite) Headache Body Ache

two filoviruses

Filoviruses are negative sense RNA viruses. There are no dsRNA viruses. Both filoviruses cause viral hemorrhagic fever (VHF). a. Ebola- Zaire, Sudan, Côte d'Ivoire, Bundibugyo, Reston b. Marburg

Macules

Flat colored spots

the replication cycle of Hepatitis B virus

HBV has a distinctly defined tropism for the liver - because small genome and HBV replicates through an RNA intermediate and produces and releases antigenic decoy particles (HBsAg). The attachment of HBV to hepatocytes is mediated by the HBsAg glycoproteins. HBsAg binds to polymerized human serum albumin and other serum proteins; binding and uptake of these proteins may facilitate virus uptake by the liver. On penetration into the cell, the partial DNA strand of the genome is completed by being formed into a complete double-stranded DNA circle, and the genome is delivered to the nucleus. Transcription of the genome is controlled by cellular transcription elements found in hepatocytes. Replication of the genome utilizes the larger-than-genome 3500-base mRNA. This is packaged into the core nucleocapsid that contains the RNA-dependent DNA polymerase (P protein). This polymerase has reverse transcriptase and ribonuclease H activity, but HBV lacks the integrase activity of the retroviruses. The 3500-base RNA acts as a template, and negative-strand DNA is synthesized using a protein primer from the P protein, which remains covalently attached to the 5′ end. After this, the RNA is degraded by the ribonuclease H activity as the positive-strand DNA is synthesized from the negative-sense DNA template. This process is interrupted by envelopment of the nucleocapsid at HBsAg-containing intracellular membranes, thereby capturing genomes containing RNA-DNA circles with different lengths of RNA. Continued degradation of the remainder of the RNA in the virion yields a partly double-stranded DNA genome. The virion is then released from the hepatocyte by exocytosis without killing the cell, not by cell lysis.

Acute Infection

HBV infection is characterized by a long incubation period and an insidious onset. Symptoms during the prodromal period may include fever, malaise, and anorexia, followed by nausea, vomiting, abdominal discomfort, and chills. The classic icteric symptoms of liver damage (e.g., jaundice, dark urine, pale stools) follow soon thereafter. Recovery is indicated by a decline in the fever and renewed appetite.

role of the Hepatitis B surface antigen in disease progression and resolution

HBsAg and HBeAg are secreted into the blood during viral replication. The detection of HBeAg is the best correlate to the presence of infectious virus. Chronic infection can be distinguished by the continued finding of HBeAg, HBsAg, or both, and a lack of detectable antibody to these antigens. Antibody to HBsAg indicates resolution of infection or vaccination. Antibody to HBcAg indicates current or prior infection by HBV and IgM anti-HBc is the best way to diagnose a recent acute infection, especially during the period when neither HBsAg nor anti-HBs can be detected (the window). Detection of antibodies to HBeAg and HBsAg is obscured during infection because the antibody is complexed with antigen in the serum. The serologic events associated with the typical course of acute hepatitis B disease. B, Development of the chronic hepatitis B virus carrier state. Routine serodiagnosis is difficult during the hepatitis B surface antigen (HBsAg) window, when HBs and anti-HBs are undetectable. Anti-HBc, Antibody to hepatitis B core antigen [HBcAg]; Anti-HBe, antibody to hepatitis Be antigen [HBeAg]; Anti-HBs, antibody to HBsAg.

time course and stages of HIV infection

HIV infection (acute phase, 2 to 4 weeks after infection) may resemble those of influenza or infectious mononucleosis, with "aseptic" meningitis or a rash occurring up to 3 months after infection. As in EBV mononucleosis, the symptoms stem from T-cell responses triggered by a widespread infection of antigen-presenting cells (macrophages). These symptoms subside spontaneously after 2 to 3 weeks and are followed by a period of asymptomatic infection or a persistent generalized lymphadenopathy that may last for several years. During this period, the virus is replicating in the lymph nodes. Deterioration of the immune response is indicated by increased susceptibility to opportunistic pathogens, especially those controlled by CD4 T cells, activated macrophages, CD8 T cells, and DTH responses (e.g., yeasts, herpes and other DNA viruses, or intracellular bacteria). The onset of symptoms correlates with a reduction in the number of CD4 T cells to less than 350/µl and increased levels of virus (as determined by polymerase chain reaction [PCR]-related techniques) and protein p24 in the blood. Full-blown AIDS occurs when the CD4 T-cell counts are less than 200/µl (oftentimes to 50/µl or undetectable), and virus load is greater than 75,000 copies/ml and involves the onset of more significant diseases, including HIV wasting syndrome (weight loss and diarrhea for more than 1 month) and opportunistic infections, malignancies, and dementia. Neutralizing antibodies are generated against gp120. Antibody-coated virus is infectious, however, and is taken up by macrophages. CD8 T cells are critical for controlling HIV disease progression. CD8 T cells can kill infected cells by direct cytotoxic action and can produce suppressive factors that restrict viral replication, including chemokines that also block the binding of virus to its co-receptor. Individuals with certain MHC types (human leukocyte antigen [HLA] B27 or B57) will preferentially bind HIV peptides rather than cellular peptides, to make infected cells better targets for CD8 T killing, and they are more resistant to HIV disease. However, CD8 T cells require activation by CD4 T cells, CD8 T-cell numbers decrease with decreasing CD4 T-cell number, and their reduction correlates with and is an indicator of disease progression to AIDS

The three genera can be distinguished by the activities of the viral attachment protein (Paramyxoviruses)

HN of parainfluenza virus and mumps virus binds to sialic acid and has hemagglutinin and neuraminidase activity, H of measles virus binds protein receptors and is also a hemagglutinin, but G of RSV (respiratory syncytial virus) binds but is not a hemagglutinin.

structure of Papillomaviruses and Polyomaviruses

Icosahedral capsid: 50-55 nm in diameter Double stranded circular genome (codes for 7 or 8 genes) 100 different types

two types of vaccines used to prevent polio

Inactivated polio vaccine (IPV) -(developed by Jonas Salk) Live attenuated oral polio vaccine (OPV)- (developed by Albert Sabin) Both induce a protective antibody response get more info on this!

the clinical syndromes associated with influenza infections

Incubation: ~14 days Symptoms: (last 1 week) Abrupt onset of fever (102-1040) Headache Myalgia (aches) Sore throat Non-productive cough NO runny nose! Cough and malaise last 2 weeks after other symptoms have resolved NO viremia (viruses in blood) Cellular damage is a results on immune system! Viruses affect ciliated cells of respiratory lining Mucus is not being moved and puts pt's at risk for a bacterial infection Secondary bacterial pneumonia is common (S. pneumoniae or S. aureus) Diagnosis: Based on symptoms Rapid test (99% specific for type A and B) Treatment: Mild cases: symptomatic care Fluids and Tylenol (for fever) DO NOT give children asprin >> Reyes syndrome) Severe cases: Antiviral drugs (see LO #8)

HHV8

Kaposi sarcoma

Control Viral Infection

Limiting personal contact with sources of infection § Gloves, masks, goggles, quarantine o Improving hygiene, sanitation, disinfection o Immunizations o Educate the public to avoid high-risk behavior

symptoms and clinical outcomes of acute hepatitis and chronic hepatitis

Major determinants of acute and chronic hepatitis B virus (HBV) infection. HBV infects the liver but does not cause direct cytopathology. Cell-mediated immune lysis of infected cells produces the symptoms and resolves the infection. Insufficient immunity can lead to chronic disease. Chronic HBV disease predisposes a person to more serious outcomes. Purple arrows indicate symptoms; green arrows indicate a possible outcome.

three mechanisms by which measles causes encephalitis

Measles can cause encephalitis in three ways: (1) direct infection of neurons; (2) a postinfectious encephalitis, which is believed to be immune mediated; and (3) subacute sclerosing panencephalitis (SSPE) caused by a defective variant of measles generated during the acute disease. The SSPE virus acts as a slow virus and causes symptoms and cytopathologic effect in neurons many years after acute disease

syncytia (multinucleated giant cells forms from viral fusion of individual cells)

Measles, HSV, VZV, HIV promote formation

Cellular receptors for picornaviruses

Most rhinoviruses bind to the intercellular adhesion molecule-1 (ICAM-1); this receptor is expressed on endothelial cells, fibroblasts, and epithelial cells Coxsackie viruses bind to decay accelerating factor (CD55) Poliovirus binds to PVR/CD155 (this is present on many different human cells)

symptoms and possible complications caused by mumps virus

Mumps infections are often asymptomatic. Clinical illness manifests as a parotitis that is almost always bilateral and accompanied by fever. Onset is sudden. Oral examination reveals redness and swelling of the ostium of the Stensen (parotid) duct. The swelling of other glands (epididymoorchitis, oophoritis, mastitis, pancreatitis, and thyroiditis) and meningoencephalitis may occur a few days after the onset of the viral infection but can occur in the absence of parotitis. The swelling that results from mumps orchitis may cause sterility. Mumps virus involves the central nervous system in approximately 50% of patients; 10% of those affected may exhibit mild meningitis with 5 per 1000 cases of encephalitis.

Prodrome

Non-specific symptoms Symptoms are caused by tissue damage and systemic effects caused by the virus and the immune system- can continue all the way through convalescence Headache, nausea, vomiting, malaise, fever

Endocytosis

Normal process used by cell for uptake of receptor-bound molecules Most nonenveloped viruses enter cell via receptor-mediated endocytosis or viropexis after VAP has interacted with cellular receptor

Enveloped virus

Nucleocapsid + glycoproteins & membrane

virus:

Obligate intracellular parasites that depend on the biochemical machinery of the host cell for replication

clinical disease caused by parainfluenza virus

Parainfluenza viruses 1, 2, and 3 may cause respiratory tract syndromes ranging from a mild cold-like upper respiratory tract infection (coryza, pharyngitis, mild bronchitis, wheezing, and fever) to bronchiolitis and pneumonia. Older children and adults generally experience milder infections than those seen in young children, although pneumonia may occur in the elderly A parainfluenza virus infection in infants may be more severe than infections in adults, causing bronchiolitis, pneumonia, and most notably croup (laryngotracheobronchitis). Croup results in subglottal swelling, which may close the airway. Hoarseness, a "seal bark" cough, tachypnea, tachycardia, and suprasternal retraction develop in infected patients after a 2- to 6-day incubation period. Most children recover within 48 hours. The principal differential diagnosis is epiglottitis caused by Haemophilus influenzae

DNA viruses

Parvovirus Papovavirus Hepadnavirus Adenovirus Herpesvirus Poxvirus

latent period

Period during which extracellular infectious virus is not detected Includes the eclipse period and ends with the release of new viruses

RNA Viruses

Picornaviruses, Togaviruses, Flaviviruses, Caliciviruses, and Coronaviruses Orthomyxoviruses, Paramyxoviruses, Rhabdoviruses, Filoviruses, and Bunyaviruses Reoviruses Retroviruses

role of PrPSc in disease pathogenesis

Prion consists of aggregates of protease-resistant, hydrophobic glycoprotein termed PrPSc(27000 to 30000 Da). Humans encode a protein termed PrPC which has a closely related or almost identical structure and the function of which is unknown but is held between the terminal serine and a glycophosphatidylinositol of the cell membrane (1). PrPC acquires the conformation of PrPSc (2). The cell synthesizes new PrPC (3), and a chain is built along cell surface anionic glycosaminoglycans (4). The chain breaks upon phagocytosis or from shear forces and releases PrPSc aggregates that act like seed crystals to start the cycle over. A form of PrPSc is internalized by neuronal cells and accumulates This causes spongiform encephalopathy where neurons lose function and there is lack of immune response or inflammation Characterized by -vacuolation of neurons and glial cells -formation of amyloid-containing plaques and fibrils -proliferation and hypertrophy of astrocytes PrPSc is taken up by neurons and phagocytic cells but is difficult to degrade, a feature that may contribute to the vacuolation of the brain tissue. Prions reach high concentrations in the brain, further contributing to the tissue damage. Prions can also be isolated from tissue other than the brain, but only the brain shows any pathologic changes. No inflammation or immune response to the agent is generated, distinguishing this disease from classic viral encephalitis. A protein marker (14-3-3 brain protein) can be detected in the cerebrospinal fluid of symptomatic persons, but this is not specific for prion disease.

Define prion and how this infectious agent differs from viruses

Prion is a slow virus agent or a small infectious, proteinaceous agent that is involved in a variety of neurodegenerative diseases Differs from viruses: -no virion structure or genome -elicit no immune response -extremely resistant to inactivation by heat, disinfectants, and radiation Basically very deadly!

Reduce the spread of viral infections

Proper sanitation Education Lifestyle changes Elimination of the arthropod or its ecologic niche Example- drain swamps The best way to limit viral spread is to immunize the population Natural infection or vaccination

vaccine for Hepatitis A virus

Prophylaxis with immune serum globulin given before or early in the incubation period (i.e., less than 2 weeks after exposure) is 80% to 90% effective in preventing clinical illness. Killed HAV vaccines have been approved by the U.S. Food and Drug Administration (FDA) and are available for all children and for adults at high risk for infection, especially travelers to endemic regions. The vaccine is administered to infants at 2 years of age and can be administered with the HBV vaccine to adults. There is only one serotype of HAV, and HAV infects only humans, factors that help ensure the success of an immunization program.

Properties of RNA Viruses

RNA is labile and transient. Most RNA viruses replicate in the cytoplasm. Cells cannot replicate RNA. RNA viruses must encode an RNA-dependent RNA polymerase. The genome structure determines the mechanism of transcription and replication. RNA viruses are prone to mutation. The genome structure and polarity determine how viral messenger RNA (mRNA) is generated and proteins are processed. RNA viruses, except for (+) RNA genome, must carry polymerases. All (−) RNA viruses are enveloped.

RSV Clinical Syndromes

RSV can cause any respiratory tract illness, from a common cold to pneumonia (Table 56-4). Upper respiratory tract infection with prominent rhinorrhea (runny nose) is most common in older children and adults. A more severe lower respiratory tract illness, bronchiolitis, may occur in infants. Because of inflammation at the level of the bronchiole, there is air trapping and decreased ventilation. Clinically, the patient usually has low-grade fever, tachypnea, tachycardia, and expiratory wheezes over the lungs. Bronchiolitis is usually self-limited, but it can be a frightening disease to observe in an infant. It may be fatal in premature infants, persons with underlying lung disease, and immunocompromised people.

Western equine encephalitis

Recombination of eastern equine encephalitis and Sinbis, both alphaviruses.

replication of the Herpesviruses

Replication and capsid assembly occurs in the nucleus. The virus is released by exocytosis, cell lysis, and through cell-to-cell bridges Viral-encoded DNA polymerase (target of antiviral drugs) replicates the viral genome Viral-encoded scavenging enzyme provide deoxyribonucleotide substrates for the polymerase Transcription of the viral genome and viral protein synthesis proceeds in a coordinated and regulated manner in three phases: leading to cell death and lytic infection 1. Immediate early proteins (α), consisting of proteins important for the regulation of gene transcription and takeover of the cell 2. Early proteins (β), consisting of more transcription factors and enzymes, including the DNA polymerase 3. Late proteins (γ), consisting mainly of structural proteins, which are generated after viral genome replication has begun

HHV7

Roseola (Exanthem subitum) - common in children. Rapid onset fever for a few days followed by a rash on the trunk and face that spreads and lasts 24-48 hrs

Structure of reoviruses

Rotaviruses and reoviruses share many structural, replicative, and pathogenic features. Reoviruses and rotaviruses have an icosahedral morphology with a double-layered capsid (60 to 80 nm in diameter) and a double-stranded segmented genome ("double:double"). The name rotavirus is derived from the Latin word rota, meaning "wheel,"which refers to the virion's appearance in negative-stained electron micrographs Proteolytic cleavage of the outer capsid (as occurs in the gastrointestinal tract) activates the virus for infection and produces an intermediate/infectious subviral particle (ISVP). The outer capsid is composed of structural proteins, which surround a nucleocapsid core that includes enzymes for RNA synthesis and 10 (reo) or 11 (rota) different double-stranded RNA genomic segments. For rotavirus, the outer capsid has two layers, an intermediate layer consisting of the major capsid protein (VP6) and an outer layer that contains the viral attachment protein (VP4) and glycoprotein (VP7). As for the influenza virus, reassortment of gene segments can occur and thus create hybrid viruses. Of interest, rotaviruses resemble enveloped viruses in that they (1) have glycoproteins (VP7, NSP4) that are on the outside of the virion, (2) acquire but then lose an envelope during assembly, and (3) appear to have a fusion protein activity that promotes direct penetration of the target cell membrane. The genomic segments of rotaviruses and reoviruses encode structural and nonstructural proteins. The genomic segments of reovirus, the proteins they encode, and their functions are summarized in those of rotavirus are summarized in Table 59-3. Core proteins include enzymatic activities required for the transcription of messenger RNA (mRNA). They include a 5′-methylguanosine mRNA capping enzyme and an RNA polymerase. The σ1 protein (reo) and VP4 (rota) are located at the vertices of the capsid and extend from the surface like spike proteins. They have several functions, including viral attachment and hemagglutination, and they elicit neutralizing antibodies. VP4 is activated by protease cleavage into VP5 and VP8 proteins, exposing a structure similar to that of the fusion proteins of paramyxoviruses. Its cleavage facilitates productive entry of the virus into cells.

prevention of rotavirus infections

Rotaviruses are acquired very early in life. Their ubiquitous nature makes it difficult to limit the spread of the virus and infection. Hospitalized patients with disease must be isolated to limit spread of the infection to other susceptible patients. No specific antiviral therapy is available for a rotavirus infection. The morbidity and mortality associated with rotavirus diarrhea result from dehydration and electrolyte imbalance. The purpose of supportive therapy is to replace fluids so that blood volume and electrolyte and acid-base imbalances are corrected. Development of a safe rotavirus vaccine was a high priority for protecting children, especially those in underdeveloped countries, from potentially fatal disease. Animal rotaviruses, such as the rhesus monkey rotavirus and the Nebraska calf diarrhea virus, share antigenic determinants with human rotaviruses and do not cause disease in humans. A human-rhesus monkey reassortant vaccine (Rotashield) was recalled in 1999 because of the incidence of intussusception (misfolding of the bowel possibly resulting from inflammatory reactions to the vaccine) in a small number of infants. Two new safer rotavirus vaccines have since been developed and are U.S. Food and Drug Administration-approved in the United States and elsewhere. RotaTeq consists of five reassortant bovine rotaviruses containing the VP4 or VP7 of five different human rotaviruses. The RotaRix vaccine is a single-strain attenuated human rotavirus. The vaccines are administered as young as possible, at 2, 4, and 6 months of age.

risk population and clinical disease of rotavirus infection

Rotaviruses are ubiquitous worldwide, with 95% of children infected by 3 to 5 years of age (Box 59-3). Rotaviruses are passed from person to person by the fecal-oral route. Maximal shedding of the virus occurs 2 to 5 days after the start of diarrhea but can occur without symptoms. The virus survives well on fomites (e.g., furniture and toys) and on hands because it can withstand drying. Although domestic animals (e.g., cows) are known to harbor serologically related rotaviruses, they are not a common source of human infection. Outbreaks occur in preschools and daycare centers and among hospitalized infants.

distribution and symptoms of SARS

SARS is a form of atypical pneumonia Symptoms: high fever (>38 degrees C), chills, rigors, headache, dizziness, malaise, myalgia, cough, difficulty breathingà acute respiratory distress syndrome Geographic distribution: Guangdong Province (South China); brought to Hong Kong, Vietnam, and Toronto by travelers

nomenclature (classification) of influenza viruses

Serotype: based on the HA and NA phenotype Ex. H1N1 Nomenclature: (virus type) / where it was isolated / day of year isolated/ year isolated / serotype Ex. A/Bankok/1/79/ (H3N2) Influenza A Isolated in Bankok in Jan of 1979 Serotype H3N2

Unique properties of parvoviruses

Smallest DNA virus Naked icosahedral capsid Single-stranded (+ or - sense) DNA genome Requires growing cells (B19) or helper virus (dependovirus) for replication Parvoviruses must infect mitotically active cells (do not encode polymerase and cannot stimulate cell growth) B19 usually replicates in erythroid cells (such as bone marrow cells) Single stranded DNA viral genome is internalized and cellular DNA polymerases are used to generate complementary DNA strand Virion is assembled in the nucleus and is released on cell lysis

Disease Mechanisms of Poxvirus

Smallpox is initiated by respiratory tract infection and is spread mainly by the lymphatic system and cell-associated viremia. Molluscum contagiosum and other poxviruses are transmitted by contact. Virus may cause initial stimulation of cell growth and then cell lysis. Virus encodes immune evasion mechanisms. Cell-mediated immunity and humoral immunity are important for resolution. Most poxviruses share antigenic determinants, allowing preparation of "safe" live vaccines from animal poxviruses.

Acute Phase

Specific symptoms Important for diagnosis

Nosocomial spread

Spread of disease in a healthcare facility/ hospital Still use quarantine

role of penton fibers in binding and pathogenesis

The adenovirus genome is a linear, double-stranded DNA with a terminal protein (molecular mass, 55 kDa) covalently attached at each 5′ end. The virions are nonenveloped icosadeltahedrons with a diameter of 70 to 90 nm. The capsid comprises 240 capsomeres, which consist of hexons and pentons. The 12 pentons, which are located at each of the vertices, have a penton base and a fiber. The fiber contains the viral attachment proteins and can act as a hemagglutinin. The penton base and fiber are toxic to cells. The pentons and fibers also carry type-specific antigens. Some adenoviruses use the class I major histocompatibility complex (MHC I) molecule as a receptor. Then the penton base interacts with an αv integrin to promote internalization by receptor-mediated endocytosis in a clathrin-coated vesicle. The virus lyses the endosomal vesicle, and the capsid delivers the DNA genome to the nucleus. The penton and fiber proteins of the capsid are toxic to the cell and can inhibit cellular macromolecular synthesis.

criteria for a diagnosis of AIDS

The major determinant in the pathogenesis and disease caused by HIV is the virus tropism for CD4-expressing T cells and myeloid cells. HIV-induced immunosuppression (AIDS) results from a reduction in the number of CD4 T cells, which decimates the helper and delayed-type hypersensitivity (DTH) functions of the immune response. During sexual transmission, HIV infects a mucosal surface, enters, and rapidly infects cells of the mucosal-associated lymphoid tissue (MALT). The initial stages of infection are mediated by M-tropic viruses, which bind to CD4 and the CCR5 chemokine receptors on dendritic and other monocyte-macrophage lineage cells, as well as memory, TH1 and other CD4 T cells. Individuals who are deficient in the CCR5 receptor are also resistant to HIV infection, and CCR5 binding is a target for an antiviral drug. HIV can also bind and remain on the surface of dendritic cells (including follicular DCs) through a lectin molecule, DC-SIGN. CD4 T cells are infected by the bound virus or by cell to cell transmission upon binding to the DC. Macrophages, DCs, memory T cells, and hematopoetic stem cells are persistently infected with HIV and are the major reservoirs and means of distribution of HIV (Trojan horse). Development of the symptoms of AIDS correlates with increased release of virus into the blood, an increase in T-tropic virus, and a decrease in CD4 T cells, with a subsequent decrease in total T-cell numbers (CD3-bearing cells) because of the lack of helper function. HIV induces several cytopathologic effects that may kill the infected T cell. These include increased permeability of the plasma membrane, syncytia formation, and induction of apoptosis (programmed cell death) resulting from an accumulation of nonintegrated circular DNA copies of the genome in nonpermissive CD4 T cells.

replication of reovirus

The replication of reoviruses and rotaviruses starts with ingestion of the virus (Figure 59-4). The virion outer capsid protects the inner nucleocapsid and core from the environment, especially the acidic environment of the gastrointestinal tract. The complete virion is then partially digested in the gastrointestinal tract and activated by protease cleavage and loss of the external capsid proteins (σ3/VP7) and cleavage of the σ1/VP4 protein to produce the ISVP. The σ1/VP4 protein at the vertices of the ISVP binds to sialic acid-containing glycoproteins on epithelial and other cells. Additional receptors include the β-adrenergic receptor for reovirus and integrin molecules for rotavirus. The σ1/VP4 of rotavirus also promotes the penetration of the virion into the cell. Whole virions of reovirus and rotavirus can also be taken up by receptor-mediated endocytosis.

Replication of herpes simplex virus, a complex enveloped DNA virus

The virus binds to specific receptors and fuses with the plasma membrane. The nucleocapsid then delivers the DNA genome to the nucleus. Transcription and translation occur in three phases: immediate early, early, and late. Immediate early proteins promote the takeover of the cell; early proteins consist of enzymes, including the DNA-dependent DNA polymerase; and the late proteins are structural and other proteins, including the viral capsid and glycoproteins. The genome is replicated before transcription of the late genes. Capsid proteins migrate into the nucleus, assemble into icosadeltahedral capsids, and are filled with the DNA genome. The capsids filled with genomes bud through the nuclear and endoplasmic reticulum (ER) membranes into the cytoplasm, acquire tegument proteins, and then acquire their envelope as they bud through the viral glycoprotein-modified membranes of the trans-Golgi network. The virus is released by exocytosis or cell lysis. GA, Golgi apparatus.

Burst size

The yield of infectious virus per cell Each infected cell may produce as many as 100,000 particles; however, only 1% to 10% of these particles may be infectious Most released particles are noninfectious (defective particles) resulting from mutation & errors in manufacture & assembly of virions

transmission of flu

Transmission: inhalation or respiratory droplet -Seasonal: Jan-Mar -HA binds sialic acid and is phagocytosed. -M2 protein drops pH in endosome to about 5.5 -Nucleocapsid are released into cytoplasm

Hemagglutinin

VAPs that also bind to erythrocytes Derives its name from its activity: agglutinate (clump together) RBCs → compromises function of RBCs

role of VP4, VP7, and NSP4

VP4 and VP7 covered under structure and replication The NSP4 protein of rotavirus acts in a toxin-like manner to promote calcium ion influx into enterocytes, release of neuronal activators, and a neuronal alteration in water absorption. The loss of fluids and electrolytes can lead to severe dehydration and even death if therapy does not include electrolyte replacement. Of interest, the diarrhea also promotes spread and transmission of the virus. Immunity to infection requires the presence of antibody, primarily immunoglobulin A (IgA), in the lumen of the gut. Antibodies to the VP7 and VP4 neutralize the virus. Actively or passively acquired antibody (including antibody in colostrum and mother's' milk) can lessen the severity of disease but does not consistently prevent reinfection. In the absence of antibody, the inoculation of even small amounts of virus causes infection and diarrhea. Infection in infants and small children is generally symptomatic, whereas in adults, it is usually asymptomatic.

Hepatitis B virus

Vaccination is recommended for infants, children, and especially people in high-risk groups. For newborns of HBsAg-positive mothers and people accidentally exposed either percutaneously or permucosally to blood or secretions from an HBsAg-positive person, vaccination is useful even after exposure. Immunization of mothers should decrease the incidence of transmission to babies and older children, also reducing the number of chronic HBV carriers. Prevention of chronic HBV will reduce the incidence of PHC. The HBV vaccines form virus-like particles. The initial HBV vaccine was derived from the 22-nm HBsAg particles in human plasma obtained from chronically infected people. The current vaccine was genetically engineered by the insertion of a plasmid containing the S gene for HBsAg into a yeast, Saccharomyces cerevisiae. The protein self-assembles into particles, which enhances its immunogenicity. The vaccine must be given in a series of three injections, with the second and third given 1 and 6 months after the first. The single serotype and limited host range (humans) help ensure the success of an immunization program.

Syncytia

Viral induced cell-to-cell fusion Causes cells to merge into multinucleated giant cells (syncytia) Become huge virus factories Used by some herpesviruses, retroviruses, & paramyxoviruses Allow virus to escape antibody detection while still allowing transmission between cells

Pathogenesis of HPV

Virus is acquired by close contact and infects the epithelial cells of the skin or mucous membranes. Tissue tropism and disease presentation depend on the papillomavirus type. Virus persists in the basal layer and then produces virus in terminally differentiated keratinocytes. Viruses cause benign outgrowth of cells into warts. HPV infection is hidden from immune responses and persists. Warts resolve spontaneously, possibly as a result of immune response. Certain types are associated with dysplasia that may become cancerous with the action of cofactors. DNA of specific HPV types is present (integrated) in the tumor cell chromosomes. - cervical carcinomas: 70% are HPV-16 or HPV-18 - E5,E6,E7 of HPV-16 and 18 are oncogenes - E5: enhances cell growth by stabilizing growth factor receptor. cell becomes more sensitive to signals - E6 (p53- inactivation of it makes cell more susceptible to mutation, etc) and E7 (inactivates p105): bind and prevent function of the cellular growth suppressor proteins

cellular co-receptors of HIV

Virus receptor is the initial determinant of tissue tropism. Binding to the receptor is the major determinant of tissue tropism and host range for a retrovirus · The co-receptor used upon initial infection of an individual is CCR5, which is expressed on myeloid, peripheral, and subsets of helper T cells (macrophages, [M]-tropic). · Later, during chronic infection of a person, the env gene mutates so that the gp120 binds to a different chemokine receptor (CXCR4), which is expressed primarily on T cells (T-tropic). · Binding to the chemokine receptor brings the viral envelope and cell plasma membrane close together and allows the gp41 to interact with and promote the fusion of the two membranes. · Binding to CCR5 and gp41-mediated fusion are targets for antiviral drugs. Human immunodeficiency virus can also bind to a cellular adhesion molecule, α-4 β-7 integrin, present on gut-associated lymphoid tissue (GALT), and dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) on dendritic and other cells. · Mutation in the env gene for the gp120 shifts the tropism of the virus from M-tropic (R5) to T-tropic (X4 virus). The gp120 of the T-tropic virus binds to CD4 and the CXCR4 chemokine receptor. Some viruses may use both receptors (R5X4 viruses). The change in receptor preference to CXCR4 occurs late and correlates with progression of disease.

Acute Respiratory Disease

a syndrome consisting of fever, runny nose, cough, pharyngitis, and possible conjunctivitis The high incidence of infection of military recruits stimulated the development and use of a vaccine for these serotypes

diagnosis of rabies virus infections

a. If given early enough, antibody administration can block the progression of the disease. Naturalizing antibody response does not happen until late in the disease when the disease has already reached the CNS. i. The delay in antibody response makes serological diagnosis unreliable. ii. Diagnosis is made based on history but is not definitive until postmortem tests can be performed. iii. Aggregates of viral nucleocapsids in Negri bodies are diagnostic iv. Samples of saliva can be tested by PCR with pretty good results. v. ELISA is used to test CSF but since antibodies aren't usually detected until late in the disease this is not a good method for early diagnosis. b. The vaccine can also be given postexposure as a form of treatment. c. Negri bodies have been described in previous objectives. The virus is not cytolytic and causes little tissue damage other than the presence of Negri bodies. Once symptoms appear treatment is supportive care. Ribavirin (guanosine analogue) has been used with one documented surviving case.

transmission and pathogenesis of rabies virus infection

a. Infection usually occurs from the bite of a rabid animal b. Rabies infection causes secretion of the virus into the animal's saliva, in addition to aggressive behavior promoted by the virus. i. Rabies can also be transmitted through the inhalation of aerosolized virus. c. Quiet replication happens for days to months until the virus can travel retrograde in axons to the dorsal root ganglia and infect the CNS. d. Incubation period (prodrome) depends on size and location of inoculum. Onset of the neurologic phase varies. Viruses often produce very similar symptoms in the prodrome phase because the symptoms are usually caused by interferon production. Differentiation is not usually possible during prodrome period. e. The most classic symptom is hydrophobia f. Other generalized symptoms occur including itching at the site of the bite, gastrointestinal symptoms, fatigue, and anorexia. Eventually, late phase a coma results. The virus is almost always fatal if untreated.

Chikungunya (transmitted by the Aedes mosquito)

a. Meaning 'that which bends up' referring to the contorted posture of infected patients b. Personally, if you decide to live in the South, I'd recommend investing in deet infused clothing. The distribution of the Aedes mosquito is moving up from South America and this virus has already been contracted within the US. Togaviruses (+ssRNA, enveloped viruses)

Sinbis

a. One segment of RNA genome codes nonstructural proteins @5' end b. The other separate segment codes for spike proteins on the outer membrane (E1,2,3). Note: the two segments are actually a part of the same genome but are separated by a hairpin loop that affects the way they are translated.

early phase

a. Recognition of target cell - using VAPs b. Attachment à Viral attachment structure may be part of capsid or protein extending off capsid c. Penetration - move into plasma membrane after being taken up by cell i. Interaction between multiple VAPs and cellular receptors initiate internalization of virus into cell ii. Nonenveloped viruses enter via receptor-mediated endocytosis OR viropexis 1. Viropexis: Hydrophobic structures of capsid proteins may be exposed after viral binding to the cells, and these structures help the virus or the viral genome slip through (direct penetration) the membrane. iii. Enveloped viruses fuse their membrane with cellular membrane to deliver nucleocapsid internally d. Uncoating - uncoat genome into cytoplasm (outside nucleocapsid or envelope) & if necessary deliver to nucleus i. Uncoating of genome abolishes infectivity & identifiable structure ii. DNA viruses must be delivered to nucleus, RNA viruses are predominantly replicated in cytoplasm

structure and replication of rabies virus - know the cell receptor

a. Rhabdoviruses are negative sense single stranded enveloped RNA viruses. b. To replicate the viral genome, an RNA dependent RNA polymerase must copy the -ssRNA genome to make +ssRNA. c. RNA polymerase can copy the +ssRNA strands to make multiple copies of the -ssRNA genome. The +ssRNA is also required to make +mRNA strands that can function as viral mRNA translated into viral proteins by host ribosomes. d. The viral structure itself is bullet shaped and the genome is non-segmented and codes for 5 proteins which are transcribed in Negri bodies: i. M protein in the matrix ii. L protein (most of the time if they call it an L protein it's a polymerase. RNA viruses have to come with their own polymerase if they are negative sense because our cells don't recognize negative sense RNAs) iii. G protein (attachment protein hooks onto nicotinic acetylcholine receptor, AChR and the virus is endocytosed. The neural cell adhesion molecule is also involved in endocytosis.) G=glycoprotein iv. Nucleoprotein (N) v. Nonstructural protein (NS) e. When the virus is endocytosed, it fuses with the membrane of an endosome and the vesicle is acidified. This allows the virus to uncoat and release the nucleocapsid into the cytoplasm. f. All negative sense single stranded RNA molecules will replicate in the cytoplasm where the ribosomes are easy to get to. g. The G protein is synthesized on membrane bound ribosomes so it can be processed in the ER/Golgi. The protein has a targeting sequence that sends it to the cell membrane in membrane vesicles h. Nucleocapsids are assembled in the cytoplasm i. Then the new virions can be enveloped in the cell plasma membrane and bud away from the cell. j. Budding does not lyse the cell.

transmission, clinical symptoms and complications, and prevention of rubella.

a. Similar properties to togaviruses b. Rubella is a respiratory (transmitted in respiratory droplets) virus that does not lyse cells, but does cause a rash and arthralgia i. The rash occurs after a 14-21 day incubation period and lasts for about 3 days as a maculopapular rash. c. The onset of lymphadenopathy coincides with viremic stage. d. Congenital rubella causes cataracts and other defects like deafness and heart problems. i. Virus can persist in tissues of the lens of the eye and be shed for up to one year. e. Virus can be shed for up to 2 weeks after the onset of the rash and during the prodromal period. f. Infection or immunization produces lifelong immunity. In order for vaccination to be effective, cell mediated immunity needs to be induced. i. The vaccine is a live attenuated vaccine administered as a part of the MMR at 2 years of age. Live attenuated vaccines are not always safe for the immunocompromised. However, live attenuated vaccines are always the best at producing an immune response, in particular a cell mediated response. g. No treatment is available. The vaccine remains the best means of prevention because there is only one serotype and no reservoir.

Viral attachment protein (VAP)

a. Specific glycoproteins of enveloped viruses b. Found on surface structure of capsid or envelope to mediate interaction of virus with the target cell i. Attach to host cell receptors (membrane bound proteins, carbs, glycoproteins, or glycolipids) c. Allows for initiation of attachment and cellular penetration needed for viral replication i. Determines which cells can be infected by virus

significance of viral RNA-dependent RNA polymerase

a. The RNA virus genome must code for RNA-dependent RNA polymerases (replicases and transcriptases) because the cell has no means of replicating RNA b. Because RNA is degraded relatively quickly, the RNA-dependent RNA polymerase must be provided or synthesized soon after uncoating to generate more viral RNA, or the infection will be aborted c. Replication of the genome provides new templates for production of more mRNA and genomes, which amplifies and accelerates virus replication

post-exposure prophylaxis of rabies and the type of vaccine available

a. This is also been described some in previous objectives. b. The first protective measure is to wash the bite wound. Soap and water inactivates the virus. This needs to be followed by antirabies serum administered in a hospital. c. Our adaptive immune response is very slow to make neutralizing antibodies to rabies virus. By the time it does, the disease is already progressed too far. d. Most viruses require some level of cell mediated immunity to gain protection because of their cellular dependence. Rabies virus elicits very little cell mediated immunity. e. Antibodies are most important for immunological protection. Administering passive immunoglobulins will buy the patient time until they can mount an adaptive immune response.

characteristics used in viral nomenclature

a. Virus names may describe viral characteristics, the diseases they are associated with, or even the tissue or geographic locale where they were first identified b. Names such as picornavirus (pico, "small"; rna, "ribonucleic acid") or togavirus (toga, Greek for "mantle," referring to a membrane envelope surrounding the virus) describe the structure of the virus c. The name retrovirus (retro, "reverse") refers to the virus-directed synthesis of DNA from an RNA template, whereas the poxviruses are named for the disease smallpox, caused by one of its members d. The adenoviruses (adenoids) and the reoviruses (respiratory, enteric, orphan) are named for the body site from which they were first isolated e. Viruses can be grouped by characteristics such as: i. Structure: size, morphology, nucleic acid ii. Disease (e.g., hepatitis) iii. Target tissue (tropism) iv. Means of transmission (e.g., enteric, respiratory) v. Vector (e.g., arboviruses; arthropod-borne virus). vi. Structure: size, morphology, and nucleic acid (e.g., picornavirus [small RNA], togavirus) vii. Biochemical characteristics: structure and mode of replication viii. Host cell (host range): animal (human, mouse, bird), plant, bacteria f. The most consistent and current means of classification is by physical and biochemical characteristics, such as size, morphology (e.g., presence or absence of a membrane envelope), type of genome, and means of replication.

Syncytia

a. multiple infected cells fuse together forming a large multinucleated cell by changing the appearance and properties of the target cell i. - Cell to cell fusion may occur in the absence of new protein synthesis (fusion from without/outside) 1. Ex- paramyxoviruses ii. May require new proteins synthesis (fusion from within) 1. Ex. HSV iii. Allows the virus infection to spread from cell to cell and escape antibody detection 1. Syncytia may be fragile and susceptible to lysis a. Ex HIV syncytia also causes death of the cells

DS RNA

acts like (−) RNA. The (−) strands are transcribed into mRNAs by an RNA polymerase in the capsid. New (+) RNAs get encapsidated and (−) RNAs are made in the capsid

Influenza A (orthomyxovirus)

an example of a (−) RNA virus with a segmented genome Its envelope is lined with matrix proteins and has two glycoproteins: The hemagglutinin (HA), which is the VAP, and a neuraminidase (NA) Because it is a negative sense virus, Influenza A must carry an RNA-dependent RNA polymerase in its nucleocapsid in order for replication to occur Once the HA binds to a sialic acid on the surface of a cell the negative sense viral genome AND the RNA-dependent RNA polymerase are internalized into the cell cytoplasm: RNA-dependent RNA polymerase immediately begins using (-) sense genome to create (+) sense RNA that can be translated by host cell ribosomes for early gene protein synthesis initiating the viral replication process

Paralytic polio

appears 3 to 5 days after minor illness (biphastic) Virus spreads from anterior horn cells to motor cortex of brain Causes paralysis (severity is determined by extent of neuronal infection and which neurons are infected)

Poxviruses

are the largest, most complex viruses. Poxviruses have complex, oval to brick-shaped morphology with internal structure. Poxviruses have a linear, double-stranded DNA genome with fused ends. Poxviruses are DNA viruses that replicate in the cytoplasm. Virus encodes and carries all proteins necessary for mRNA synthesis. Virus also encodes proteins for functions such as DNA synthesis, nucleotide scavenging, and immune escape mechanisms. Virus is assembled in inclusion bodies (Guarnieri bodies; factories), where it acquires its outer membranes. Must carry many enzymes, includes DNA-dependent RNA polymerase to allow viral mRNA synthesis in the cytoplasm

Cocksackie B viruses

associated with myocarditis and pleurodynia (Bornholm disease or devil's gripà sudden onset fever and unilateral sharp intercostal muscle pain that can be excruciating; lasts about 4 days)

the outer layer of the virion is the

capsid or envelope i. These structures are the package, protection, and delivery vehicle during transmission of the virus from one host to another and for spread within the host to the target cell ii. The surface structures of the capsid and envelope mediate the interaction of the virus with the target cell through a viral attachment protein (VAP) or structure iii. Removal or disruption of the outer package inactivates the virus iv. Antibodies generated against the components of these structures prevent virus infection v. The capsid is a rigid structure able to withstand harsh environmental conditions 1. Viruses with naked capsids are generally resistant to drying, acid, and detergents, including the acid and bile of the enteric tract 2. Many of these viruses are transmitted by the fecal-oral route and can endure transmission even in sewage vi. The envelope is a membrane composed of lipids, proteins, and glycoproteins 1. The membranous structure of the envelope can be maintained only in aqueous solutions 2. It is readily disrupted by drying, acidic conditions, detergents, and solvents such as ether, which results in inactivation of the virus 3. As a result, enveloped viruses must remain wet and are generally transmitted in fluids, respiratory droplets, blood, and tissue 4. Most cannot survive the harsh conditions of the gastrointestinal tract

Adenovirus

cause lytic, persistent, and latent infections in humans

Tissue Tropism

cells and tissues of a host which support growth of a particular virus or bacteria some bacteria and viruses have a broad tissue tropism, meaning they can infect many types of cells and tissues; while other viruses may infect primarily a single tissue

Oncogenic virus

different mechanisms for immortalizing cells Activating or providing growth stimulating genes Removing the inherent braking mechanisms that limit DNA synthesis and cell growth Example- papillomavirus encode proteins that bind and inactivate cell growth and regulatory proteins Preventing apoptosis Example- Epstien Barr virus immortalizes B cells by stimulating cell growth and prevent apoptosis

Cocksackie A viruses

diseases with vesicular lesions (Herpanginaà vesicular ulcerated lesions on soft palate and uvula) (Hand-foot-and mouth diseaseà vesicular lesions on hands, feet, mouth, and tongue)

steps in viral replication

early phase late phase

Poxvirus

encodes its own polymerases and enzymes to provide deoxyribonucleotides for DNA synthesis, replication machinery, and transcription machinery in the cytoplasm.

Eclipse period

ends w/ appearance of new virions after virus assembly (like solar eclipse); time between infection and appearance of mature virus within cell

DNA probes

has sequences complementary to specific regions of a viral genome; good for slowly replicating viruses or nonproductive viruses(CMV and HPV) in situ hybridization/ FISH (with fluoresence)

Retroviruses

have (+) RNA that is converted to complementary DNA (cDNA) by reverse transcriptase carried in the virion. cDNA integrates into the host chromosome, and the host makes mRNAs, proteins, and full-length RNA genome copies.

Presence of virus without virus production but with potential for reactivation (latent-recurrent infection)

i. Persistent infections maybe: a. Chronic-nonlytic, productive b. Latent-limited viral macromolecular but no virus synthesis c. Recurrent-periods of latency then virus production d. Transforming- immortalizing ii. Side note: the nature of the infection determined by the characteristics of the virus and the target cell

Failed infection (abortive infection)

i. Viral mutants ii. Do not multiple and therefore they disappear

Cell death (lytic infection)

i. Virus replication kills the target cell by many methods 1. Induce apoptosis 2. Shut down certain parts of the cell a. Ex) shut down an important enzyme pathway 3. Damage the cell repair mechanisms

late phase

i. e. Macromolecular synthesis i. Early mRNA & nonstructural protein synthesis: 1. DNA-binding proteins (viral polymerases) 2. Need a few copies of these proteins because they are catalytic ii. Replication of genome 1. Viruses that replicate in to cytoplasm must provide their own mechanisms for mRNA processing & modification (adding 3' polyA tail & 5' methylated cap, removal of introns) iii. Late mRNA & structural protein synthesis: 1. Need many copies of these proteins to package virus iv. Posttranslational modification of proteins ii. f. Assembly of virus: i. Each part of virion has recognition structures that allow the virus to form the appropriate interactions needed to assemble final complete virion iii. g. Budding of enveloped viruses. iv. h. Release of virus. i. Enveloped viruses may also enter by steps 2′ and 3′ and assemble and exit from the cell by steps 8′ and 9′. The antiviral drugs for susceptible steps in viral replication are listed in magenta

Inclusion body

intracellular structure resulting from changes in chromosomes or membrane structure, or accumulation of viral capsid- may result from virus induced changes in the membrane or chromosomal structure or may represent the sites of viral replication or accumulation of viral capsids Example: chromosomal aberrations and degradation may occur and can be detected with histologic staining Used in diagnosis in particular infections because they are consistent and recognizable with staining

Optimum temperature range for viral growth

is 33-35 degrees C (so virus remains in localized in the upper respiratory tract)

Single-stranded DNA (SS DNA)

is converted into DS DNA and replicates like DS DNA

(−) RNA

is transcribed into mRNAs and a full-length (+) RNA template by the RNA polymerase carried in the virion. The (+) RNA template is used to make (−) RNA genome progeny.

Pathogenesis by arenaviruses

largely attributed to immunopathogenesis. · Arenaviruses are able to infect macrophages, induce cytokine and interferon release and promote cell and vascular damage. · T-cell-induced immunopathologic effects significantly exacerbate tissue destruction. · Persistent infection of rodents results from neonatal infection and the induction of immune tolerance. · The incubation period for arenavirus infections averages 10 to 14 days.

Nodules

larger (than papule) raised area of skin

Attenuation

loss of virulence factors (results in a loss of pathogenicity) Many vaccines consist of attenuated viruses

Reservoir

maintains and amplifies the virus in the environment

Disinfectant

most viruses will not survive a. 70% ethanol b. 15% bleach c. 2% glutaraldehyde d. 4% formaldehyde a. "universal" precaution when handling human blood/needles/surgical tools e. GOLD RULE: treat all guns like a loaded gun. Same goes for human samples: treat every sample likes it contaminated with HIV/HBV a. Outbreak control requires quick ID of source (food, water, daycare center/school)

Antigenic Shift

new virus subtype emerges containing a new HA and NA antigens Only occurs in type A (because it can infect animals and humans) Sudden change in HA and NA antigens means no one has immunity to the strain >>> cause Pandemic (occur about ever 10-20 yrs) o Mechanics: Two subtypes of influenza A co-infect the SAME host cell Viral RNA is resorted to create an entirely new viral genome Nomenclature: based on where it took place (ex. Swine flu, Avian flu)

Persistent infection

occurs in an infected cell that is not killed by the virus Virus is released gently by exocytosis or through budding (many enveloped viruses) from the plasma membrane

Pharyngoconjunctival fever

occurs more often in outbreaks involving older children (Ex: A 7-year-old student develops sudden onset of red eyes, sore throat, and a fever of 38.9° C (102° F). Several children in the local elementary school have similar symptoms

HSV - 2

primary target: micro ep cells site of latency: sacral gang means of spread: direct - usually sexually clinical disease: genital herpes neonatal herpes; complications = meningitis recurrent disease: genital herpes Vacc: No Cancer: No

Cytomegalovirus (CMV)

primary target: mono nuclear cells, ep cell site of latency: mononuclear cells means of spread: blood tissue, most body secretions clinical disease: mononucleosis (heterophile -), cytomegalic inclusion disease ** failed kidney transplant; hydrops fetalis recurrent disease: asymptomatic shedding lab diagnosis: cytomegalic cell with owl's eye; basophilic intranuclear inclusion body Vacc: No Cancer: medulloblastomas most common brain tumor in children

Varcilla Zoster Virus (VSV)

primary target: muco ep cells site of latency: dorsal root ganglia means of spread: inhale; infect tonsils to resp tract clinical disease: chickenpox recurrent disease: shingles (zoster) - 20-30% get possibly fatal interstital pneumonia lab diagnosis: syncytia; cowcry type A intranuclear inclusions Vacc: yes - live Oka strain Cancer: No

Epstein Barr Virus (EBV)

primary target: muco ep cells, B cells site of latency: B cells means of spread: saliva clinical disease: mononucleosis (heteophile +) recurrent disease: Asymptomatic shedding lab diagnosis: atypical t-cell (downey cell); triad, lymphadenopathy, splenomegaly, exudative pharyngitis Vacc: No Cancer: AfB1 (endemic Burkitt lymphoma), Hodgkin disease, and nasopharyngeal carcinoma, some B cell lmphomas

disease JC virus

progressive multifocal leukoencephalopathy

Oncogenes

protein products affects host cell growth regulation genes 1. Addition of viral oncogenes 2. Activation of host oncogenes 3. Inhibits tumor suppressor genes i. v. 15% human cancers related to viruses 2. Examples: a. HPV 16 and 18 = 18 uterine/ cervical b. EBV - Burkitt's lymphoma c. HBV & HCV- Liver cancer d. HHV-8 - Kaposi's sarcoma e. HTLV-1 = adult leukemia

Permissive cell

provides the biosynthetic machinery to support the complete replicative cycle of the virus

Convalescence

recovery period i. Symptoms are largely resolved ii. Infection can become persistent or chronic iii. Individuals usually develops a memory immune response for future protection against a similar challenge with the virus

BK virus (disease)

renal disease

Parvovirus

requires cells undergoing DNA synthesis to replicate

(+) RNA

resembles an mRNA that binds to ribosomes to make a polyprotein that is cleaved into individual proteins. One of the viral proteins is an RNA polymerase that makes a (−) RNA template and then more (+) RNA genome progeny and mRNAs

Latent infection

results from DNA virus infection of a cell that restricts or lacks the machinery for transcribing all the viral genes the specific transcription factors required by such a virus may be expressed only in specific tissues, in growing but not resting cells, or after hormone or cytokine induction example HSV is a latent infection in neurons that don't express the nuclear factors required to transcribe the immediate early viral genes but stress and other stimuli can activate the cells to allow viral replication

Papules

slightly raised areas; result from immune response not direct effect of virus

Antigenic Drift

small mutations in viral DNA cause minor changes in HA and NA expression, bypassing the hosts previously developed immunity to virus Viral RNA has no proofreading mechanism Occurs yearly (that's why there is a new flu vaccine every year) o Occurs in type A and B Cause Epidemic

Papovavirus

stimulates cell growth and DNA synthesis

Polyomavirus

stimulates cell growth and DNA synthesis

Hepadnavirus

stimulates cell growth, cell makes RNA intermediate, encodes a reverse transcriptase

Hepadnavirus

stimulates cell growth, cell makes RNA intermediate, encodes a reverse transcriptase.

Herpesvirus

stimulates cell growth, encodes its own polymerase and enzymes to provide deoxyribonucleotides for DNA synthesis, establishes latent infection in host

Herpesvirus

stimulates cell growth, encodes its own polymerase and enzymes to provide deoxyribonucleotides for DNA synthesis, establishes latent infection in host.

Adenovirus

stimulates cellular DNA synthesis and encodes its own polymerase

Adenovirus

stimulates cellular DNA synthesis and encodes its own polymerase.

transmission and clinical disease of Sin Nombre

supergroup of at least 200 enveloped, segmented, negative-strand RNA viruses most of the Bunyaviridae are arboviruses (arthropod-borne) spread by mosquitoes, ticks, or flies and are endemic to the environment of the vector Hantaviruses are the exception; they are carried by rodents. · Virion is enveloped with three (L, M, S) negative-sense ribonucleic acid nucleocapsids but no matrix proteins. · Virus replicates in the cytoplasm. · Virus can infect humans, animals and arthropods. · Virus in an arthropod can be transmitted to its eggs. · Sin Nombre (sub virus for hantavirus); Results in: Hantavirus pulmonary syndrome, shock, pulmonary edema: Hosts: Deer mouse. Viruses from this subfamily have been associated with outbreaks of respiratory tract disease in the eastern and western United States and Central and South America.

negative-strand RNA virus genomes

the templates for production of mRNA i. The negative-strand RNA genome is not infectious by itself, and a polymerase must be carried into the cell with the genome (associated with the genome as part of the nucleocapsid) to make individual mRNA for the different viral proteins ii. As a result, a full-length positive-strand RNA must also be produced by the viral polymerase to act as a template to generate more copies of the genome iii. The (−) RNA genome is like the negatives from a roll of movie film: each frame encodes a photo/mRNA, but a full-length positive is required for replicating the roll

Tropism

the virus has a certain tissue preference (can replace the word trophism with preference) i. Given virus may target a certain tissue ii. Tissue(s) infected determines the symptoms of the disease 1. Example 1- virus will target one specific tissue a. hepatitis targets the liver, Encephalitis targets the CNS 2. Example 2- virus may cause several different diseases or no observable symptoms a. HSV-1 can cause gingivostomatitis, pharyngitis, herpes labialis (cold sores), genital herpes, encephalitis or keratoconjunctivitis depending on affected tissue

incubation

time btwn first exposure and onset of symptoms Asymptomatic Can cause substantial damage during incubation Range from days to years

Double-stranded DNA (DS DNA)

uses host machinery in the nucleus (except poxviruses) to make mRNA, which is translated by host cell ribosomes into proteins. Replication of viral DNA occurs by semiconservative means, by rolling circle, linear, and in other ways.

Virulence Factor

viral "activities" which promote efficiency in viral replication, transmission, escape of host immune defense, access and binding of the virus to target tissue and immune resolution Essential for pathogenicity

Zoonoses

viral disease shared between animals and insects and humans Examples: bats, dogs, raccoons, foxes, cats are reservoirs and vectors for the rabies virus

Southern blot (for DNA)

viral genome or electrophoretically separated restriction endonuclease cleavage fragments of the genome are blotted onto nitrocellulose filters and then detected on the filter by their hybridization to DNA probes and Northern blot (for RNA) the method of choice: for detection, quantification, and identification of viruses uses genome amplification techniques, including PCR for DNA genomes and reverse transcriptase PCR (RT-PCR) for RNA genomes. Use of the appropriate primers for PCR can promote a millionfold amplification of a target sequence in a few hours. This technique is especially useful for detecting latent and integrated sequences of viruses, such as retroviruses, herpesviruses, papillomaviruses, and other papovaviruses, as well as evidence of viruses present in low concentrations and viruses that are difficult or too dangerous to isolate in cell culture

unique properties of human picornavirus

virion is a naked, small (25-30 nm) icosahedral capsid enclosing a single-stranded pos RNA genome enteroviruses are resistent to pH 3-9, detergents, mild sewege treatment, and heat rhinoviruses are labile at acidic pH; optimum growth temp is 33 degrees genome is a mRNA naked genome is sufficient for infection virus replicates in cytoplasm ciral RNA is translated into poluprotein, which is then cleaved into enz and structural protein most viruses are cytolytic

Virion

virus particle The units for measurement of virion size are nanometers (nm) Larger virions can hold a larger genome that can encode more proteins, and they are generally more complex

Arbovirus

viruses that are specifically arthropod borne a. Mosquitoes, ticks, fleas, louse can act as vectors for togaviruses, flaviviruses, bunyaviruses or reoviruses b. Most have very broad host range- capable of replication in specific insects, birds, amphibians, and mammals, in addition to humans c. Arboviruses must establish a viremia in the animal reservoir so that the insect can acquire the virus during its blood meal

Disease caused by Papillomavirus

warts, condylomas, papillomas, cervical cancer

transmission and clinical symptoms of parvovirus B19 infections

· B19 is transmitted by respiratory droplets and oral secretions (also possible transmission by IV blood clotting factor concentrate) · Most common in children · Infection starts with prodromal period of 7 to 10 days (person is contagious during this time) · Infection can cause no noticeable symptoms or nonspecific symptoms (sore throat, fever chills, fatigue, myalgia, decrease in Hb levels) · After this period distinctive rash appears on cheeks then rash spreads to exposed skin such as arm and legs → subsides after 1 to 2 weeks · In adults B19 infection causes polyarthritis (can have a rash or not) that can last for weeks or months · Clinical symptoms...

transmission and clinical symptoms of Norwalk virus

· Outbreaks are generally caused by a common source of contamination (ex. Water, salad, food workers) · Transmitted by fecal-oral route · Clinical symptoms...acute diarrhea, nausea, vomiting (sometimes fever and abdominal cramps). NO bloody stools. causes watery diarrhea ** noroviruses- think outbreaks on cruise ships, resorts (water, shellfish, salad, raspberries, food service)

the role of gp120, gp41, reverse transcriptase, integrase, and protease in HIV viral replication

· Replication of the human retroviruses (e.g., HIV) starts with binding of the viral glycoprotein spikes (trimer of gp120 and gp41 molecules) to the primary receptor, the CD4 protein, and a second receptor, a 7-transmembrane G-protein-coupled chemokine receptor. · Later, during chronic infection of a person, the env gene mutates so that the gp120 binds to a different chemokine receptor (CXCR4), which is expressed primarily on T cells (T-tropic). · Once the genome is released into the cytoplasm, the early phase of replication begins. The reverse transcriptase, encoded by the pol gene, uses the tRNA in the virion as a primer and synthesizes a complementary, negative-strand DNA (cDNA). · The reverse transcriptase also acts as a ribonuclease H, degrades the RNA genome, and then synthesizes the positive strand of DNA. · The reverse transcriptase is the major target for antiviral drugs. During the synthesis of the virion DNA (provirus), sequences from each end of the genome (U3 and U5) are duplicated, thus attaching the LTRs to both ends. · This process creates sequences necessary for integration and creates enhancer and promoter sequences within the LTR for the regulation of transcription. The DNA copy of the genome is larger than the original RNA. · The double-stranded cDNA is then delivered to the nucleus and spliced into the host chromosome with the aid of a virus-encoded, virion-carried enzyme, integrase. · Integration requires cell growth, but the cDNA of HIV and other lentiviruses can remain in the nucleus and cytoplasm in a nonintegrated circular DNA form until the cell is activated. Integrase is a target for an antiviral drug. · RNA-dependent DNA polymerase (reverse transcriptase), protease and integrase enzymes are carried in the virion. · Replication proceeds through a DNA intermediate termed the provirus. The provirus integrates randomly into the host chromosome and becomes a cellular gene. Transcription of the genome is regulated by the interaction of host transcription factors with promoter and enhancer elements in the long terminal repeat portion of the genome. · Simple retroviruses encode gag, pol, and env genes. Complex viruses also encode accessory genes (e.g., tat, rev, nef, vif, and vpu for HIV). · Virus assembles and buds from the plasma membrane. · Final morphogenesis of HIV requires protease cleavage of Gag and Gag-Pol polypeptides after envelopment

pathogenesis of rhinoviruses

· Rhinoviruses are cause of common cold · Receptor is ICAM-1 · Labile to acidic pH and therefore unable to replicate in GI tract · Grow best at 33 degrees C (like cooler environment of nasal mucosa) · Virus enters through nose, eyes, mouth and initiates infection in upper respiratory tract · Replication usually occurs in nose

clinical disease caused by arenaviruses

· arenaviruses include lymphocytic choriomeningitis (LCM) and hemorrhagic fever viruses, such as the Lassa, Junin, and Machupo viruses. · these viruses cause persistent infections in specific rodents and can be transmitted to humans as zoonoses · virus has enveloped virion with two circular, negative-RNA genome segments (L, S). Virion appears sandy because of ribosomes. · S genome segment is ambisense. · arenaviruses, like the hantaviruses, infect specific rodents and are endemic to the rodents' habitats. · chronic asymptomatic infection is common in these animals and leads to a chronic viremia and long-term viral shedding in saliva, urine, and feces. · Humans may become infected through the inhalation of aerosols, the consumption of contaminated food, or contact with fomites. Bites are not a usual mechanism of spread.

Pathogenesis of Sin Nombre

· viruses are spread by arthropod vector; injected into the blood to initiate a viremia. · Progression past this stage to secondary viremia and further dissemination of the virus can deliver the virus to target sites typically involved in that particular viral disease, such as the central nervous system, liver, kidney, and vascular endothelium. · bunyaviruses are good inducers of type 1 interferons. · Bunyavirus disease is due to a combination of immune and viral pathogenesis. · The incubation period for these illnesses is approximately 48 hours, and the fever typically lasts 3 days. · Initial viremia may cause flu like symptoms. · Establishment of secondary viremia may allow virus access to specific target tissues, including the central nervous system, organs, and vascular endothelium. · Antibody is important in controlling viremia; interferon and cell-mediated immunity may prevent the outgrowth of infection and contribute to disease.

laboratory methods involved in diagnosis of viral diseases

• - cytologic examination, electron microscopy, virus isolation and growth, cell culture, detection of viral proteins (antigens and enzymes), detection of viral genomes, serology (virus specific immunoglobulin IgM antibody) • **SEROCONVERSION is indicated by at least a fourfold increase in the antibody titer think PCR, RT-PCR, ELISA, Western blot (to confirm seroconversion and hence HIV infection), latex agglutination

influenza A v B

• Influenza A: • Infect humans OR animals (few infect both) • Coinfection is important for antigenic shift (discussed below) Influenza B : infect people ONLY

the general structure and genetic makeup of influenza viruses

• Influenza genera (A,B,C) • Cause acute respiratory disease • Structure: • Negative stranded RNA • Separated into 8 unique helical segments • Spherical or tubular structure (pleomorphic) • Enveloped Hemagglutinin(HA) Neuraminidase (NA) M proteins

M proteins

• M1: present inside virion, promotes virus assembly • M2: proton channel; promotes uncoating and viral • Target for antiviral drugs (against Influenza A) • NP: (nucleocapsid) promotes export of nucleocapsid to nucleus

Nonpermissive cell may lack

• Receptor • Important enzyme pathway • Transcriptional activator • Express an antiviral mechanism that will not allow replication of a particular type of strain of virus ii. § Example neurons and non-growing cells lack the machinery and substrates for replication of a DNA virus

Neuraminidase (NA)

• glycoprotein; cleaves sialic acids to prevent clumping of viruses, and facilitations spread of virus. • New antiviral drugs target and block NA function