RNA Viruses MCQ

*The answer is A.* There are no specific antiviral treatments for rotavirus infection. The most effective treatment simply involves fluid and electrolyte replacement. The virus is non-enveloped and therefore membrane fusion does not occur. Metronidazole is used to treat infections with anaerobic bacteria and some parasitic infections. Unlike HIV, rotavirus does not have reverse transcriptase or proteases that are required for virus maturation.

Appropriate treatment of rotavirus infection includes which of the following? A. Fluid and electrolyte replacement B. Antiviral drugs targeting membrane fusion C. Metronidazole D. Antiviral drugs targeting reverse transcriptase E. Antiviral drugs targeting proteolytic processing

*The answer is B.* Enteroviral meningitis, for which there is only supportive treatment, is frequently seen in late summer or early fall.

On September 17, a 22-year-old male college student appears at the Student Health Clinic complaining of moderate headache, nausea, and vomiting. His temperature is 38.5°C/101°F and his physical examination shows stiffness in the neck. What is the most likely viral cause of the symptoms? (A) CMV (B) Enterovirus (C) EBV (D) HSV type 1

*The answer is C.* The child's symptoms are those found with croup caused by parainfluenza virus.

A 4-year-old girl is brought to your rural clinic office by her mother who states the child has a runny nose, barking cough, and a sore throat. Your examination indicates respiration is labored. None of her three siblings is sick. The most probable viral cause of her symptoms is (A) Adenovirus (B) Influenza virus (C) Parainfluenza virus (D) RSV

*The answer is D.* The viruses listed above are all members of the Picornaviridae family, which includes the rhinovirus and enterovirus genera. In general, viruses are stable between pH values of 5.0 and 9.0. Once the pH drops below 5.0 (as in the stomach, which can have a pH of 1 .0), the acid-labile rhinoviruses are inactivated. Enteroviruses, in contrast, are relatively acid stable and can therefore pass through the stomach and into the small intestine without being denatured or degraded by the acid environment. This explains why enteroviruses can colonize or infect the Gl tract, whereas rhinoviruses are limited to colonization or infection of the upper respiratory tract.

Picornaviruses are small RNA-containing viruses. Which of the following picornaviruses are the most acid-labile? A. Coxsackie A B. Echovirus C. Poliovirus D. Rhinovirus E. Hepatitis A virus

*The answer is D.* Mumps is characterized by swollen parotid glands, and can be prevented with the lived-attenuated MMR vaccine.

A 10-year-old boy was sent home from school due to pain on both sides of the parotid area while eating lunch. The swelling of the glands increased in 2 to 3 days while he remained home. He complained of a headache and had a low-grade fever. This child had not received all the required vaccinations. The teacher reported that one of the other students in the classroom had had similar complaints three weeks earlier. The disease is diagnosed as which of the following? a. Measles b. Common cold c. Influenza d. Mumps e. Infectious mononucleosis

*The answer is B.* The case is descriptive of hand-foot-and-mouth disease caused by coxsackieviruses. Coxsackieviruses belong to the Enterovirus group and are transmitted by a fecal-oral route. They are common childhood infections. None of the other viruses listed cause this constellation of symptoms. Adenoviruses are associated with respiratory and diarrheal illnesses. Cytomegalovirus is associated with various diseases in the immune compromised. Papillomaviruses cause warts. Rotavirus is a cause of diarrhea.

A 14-month-old girl presents with a low-grade fever and rash on her hands and feet as seen in the accompanying photographs. Vesicular lesions were also present on the tongue, palate, and buccal mucosa. The lesions resolved spontaneously within 1 week. What is the most likely etiology of this infection? (A) Adenovirus (B) Coxsackievirus (C) Cytomegalovirus (D) Papillomavirus (E) Rotavirus

*The answer is D.* This patient's clinical presentation is consistent with measles (rubeola), which can be complicated by subacute sclerosing panencephalitis. Measles is caused by a paramyxovirus and is most common in areas with low measles vaccination rates. It typically presents with a prodrome of low-grade fever and malaise with the "3 C's:" cough, coryza (erythematous mucous membranes), and conjunctivitis. Grey-white spots on the buccal mucosa, termed Koplik spots, are usually present early in the disease course, but disappear by the time the classical measles rash appears. The classical rash is maculopapular, spreads from the face to the trunk and limbs, and spares the palms and soles. Subacute sclerosing panencephalitis is the most dangerous complication of measles infection and is thought to occur in 1:2000 cases.

A 2-year old boy is brought to a pediatrician's office by his parents. They report that the child had a low-grade fever five days ago, along with a cough and eye discharge. An eruption is seen on his face, trunk and hands, and his parents say it started about 2 days ago on his face (similar to Figure A). Oral examination is unremarkable. Which of the following is a complication of this patient's condition? A. Mitral valve disease B. Glomerulonephritis C. Hearing loss D. Encephalitis E. Recurrent dermatomal rash

*The answer is D.* Rotaviruses are the most likely cause of infant gastroenteritis.

A mother brings her 18-month-old son to your office. She was called by her day care center who reported he had vomited twice during the morning and had diarrhea as well. She noted he had a slight fever the past 2 days and had not been very hungry. The most likely cause of his illness is (A) Adenovirus (B) Astrovirus (C) Norovirus (D) Rotavirus

*The answer is C.* The case described is typical for this disease. Croup occurs most commonly in children less than 3 years of age. The symptoms, particularly the barklike cough and the steeple sign, are indicative of croup. Several respiratory viruses can cause croup; however, the most common cause is a parainfluenza virus (PIV 1, 2, or 3). Bronchiolitis and pneumonia can be ruled out due to the lack of infiltrates on chest radiographs. Epiglottitis is an inflammation of the epiglottis, most commonly bacterial in origin. It is included in the differential diagnosis of croup; however, it is a medical emergency with a distinct clinical presentation. Bronchitis is a cause of cough in young children; however, radiological findings are usually negative.

A 2-year-old girl was brought to the emergency department by frantic parents with a 3-day history of coldlike illness and a 1-day history of diffi culty breathing and an unusual, barklike cough. Physical exam revealed a fever of 38 °C, tachypnea, and tachycardia and stridor. A chest radiograph revealed narrowing of the upper airways (a steeple sign); however, lungs were free of infiltrates. A rapid antigen detection test on respiratory secretions was positive for parainfluenza virus. What is the clinical diagnosis? (A) Bronchitis (B) Bronchiolitis (C) Croup (D) Epiglottitis (E) Pneumonia

*The answer is A.* This patient most likely has Hepatitis A. This is indicated because he traveled outside of the U.S and ate from local food stands and he has mild jaundice.

A 20-year-old man comes to your clinic complaining of anorexia (loss of appetite), weight loss and fatigue for about 2 weeks. On exam you find he is mildly jaundiced and his abdomen is tender in the right upper quadrant. On further questioning, you discover he traveled outside of the United States and ate from local food stands. Serology could likely be positive for which of the following? A) IgM to Hepatitis A antigen B) IgG to Hepatitis B core antigen C) Hepatitis C surface antigen D) Hepatitis B surface antigen E) IgM to Hepatitis D antigen

*The answer is E.* Mumps vaccine, combined with measles and rubella has been in use in the United States since 1967 when it was approved by the FDA. A single dose of the live, attenuated trivalent vaccine was recommended at about 15 months of age. Children 15 months of age and even younger respond well to protein antigens. The efficacy of a single dose of MMR is 90%; thus, on a college campus of 10,000 students who received a single dose of MMR, 1,000 would still be susceptible to all three viruses. There is only a single strain of mumps virus, and the virus does not undergo rapid antigen variation. In 1989, following outbreaks of measles virus in vaccinated populations, a second dose of the vaccine was recommended for children 4 to 6 years of age.

A 21-year-old college student contracted mumps infection as did several other students at the college. He had received a single dose of the measles, mumps, rubella (MMR) vaccine at 15 months of age. What is the most likely reason that he became infected despite having been vaccinated? (A) Early vaccines only contained one of the four strains of mumps virus (B) Early versions of the mumps vaccine were heat inactivated and induced immune suppression in some recipients (C) Fifteen months of age is too early to receive the MMR vaccine (D) Mumps virus rapidly undergoes antigenic variation (E) Some individuals who receive a single dose of mumps vaccine do not respond adequately

*The answer is A.* Hepatitis A virus infection is most often silent or subclinical ("anicteric" with no jaundice observed) in children but can also present as an acute, self-limited illness characterized by jaundice malaise, fatigue, anorexia, nausea, vomiting. right upper quadrant pain, or an aversion to smoking. Clinical disease is typically less common but more severe in adults. As living conditions improve in many countries, however, a diminishing number of adults have antibodies to HAV and therefore remain susceptible to infection. It is currently estimated that 40-70% of adults within the United States have anti-HAV lgG antibodies, with most positive individuals having never experienced an icteric illness.

A 22-year-old male is found to have serum anti-HAV lgG antibodies although he denies any vaccination against hepatitis. The laboratory finding most likely indicates: A. An anicteric viral infection in the past B. An icteric illness in the childhood C. Chronic viral hepatitis D. Asymptomatic viral carrier state E. Reinfection with hepatitis A virus F. Immunity against hepatitis 0 infection

*The answer is B.* he viral protein gp120 mediates HIV attachment to host macrophages through the CCR5 and CD4 complex. The viral protein gp120 is a product of the env gene, which codes a polyprotein product that is subsequently glycosylated to form gp160. The gp160 is cleaved within host cell endoplasmic reticulum to form gp120 and gp41. gp120 binds the CXCR4 or CCR5 co-receptor and CD4 complex on T cells and the CCR5 and CD4 complex in macrophages. Homozygous CCR5 mutation confers HIV immunity, while heterozygous CCR5 mutation leads to a slower disease course in infected individuals.

A 23-year-old male with a homozygous CCR5 mutation is found to be immune to HIV infection. The patient's CCR5 mutation interferes with the function of which viral protein? A. Reverse transcriptase B. gp120 C. gp41 D. p24 E. pp17

*The answer is A.* Dengue virus, which is transmitted by mosquito bites, is present in the Caribbean and causes "breakbone fever," which is consistent with these symptoms.

A 23-year-old medical student on the Caribbean island of Dominica presents at the Student Health Clinic complaining of an increasingly severe headache and back and bone pain. Yesterday she was nauseated and vomited several times during the night. She has a 39.5°C/103°F fever, which appeared suddenly, and a generalized rash that blanches under pressure. She had been hiking in the rainforest 1 week earlier and was particularly bothered by mosquitoes at that time. The most likely infectious agent causing her symptoms is (A) Dengue virus (B) LCM virus (C) West Nile virus (D) Yellow fever virus

*The answer is A.* Outbreaks of viral conjunctivitis are common, particularly in crowded situations like camps, families, and schools. The most common viral cause is adenoviruses. This virus is able to remain viable in swimming pools particularly if they lack adequate chlorination and have noticeable organic matter that creates turbidity in the water. The other viruses listed are not common causes of conjunctivitis.

An 8-year-old boy attending 4-week summer camp presented in August with a 3-day history of fever, sore throat and conjunctivitis. Seven other children and two camp counselors developed similar symptoms over the next few days. All described a gritty feeling in their eyes. A similar outbreak had occurred at the camp in July. The cause of the outbreak of fever, sore throat, and conjunctivitis was found to be a virus traced to the camp's underchlorinated, turbid swimming pool. Which virus is the cause of this outbreak? (A) Adenovirus (B) Influenza virus (C) Parainfluenza virus (D) Respiratory syncytial virus (E) Rotavirus

*The answer is B.* Explanation: Hepatitis C virus has six or more genotypes and multiple sub genotypes, as demonstrated by the genetic differences in the encoding of its two envelope glycoproteins. This genetic variation has led to the development of a hypervariable region of the envelope glycoprotein that is especially prone to frequent mutation. Moreover, there is no proofreading 3' — 5' exonuclease activity built into the virion-encoded RNA polymerase. As a result, the RNA polymerase makes many errors during replication, with several dozen subspecies of hepatitis C virus typically present in the blood of an infected individual at any one time. Because of this remarkable variety in the antigenic structure of the HCV envelope proteins, production of host antibodies lags behind the production of new mutant strains of HCV and effective immunity against infection is not conferred. The tremendous antigenic variety of HCV has significantly slowed efforts to develop a vaccine against the virus.

A 25-year-old male with a several month history of fluctuating levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) is found to have high titers of lgG directed against hepatitis C envelope protein. These antibodies do not confer effective immunity against the infection because: A. The antibodies do not have neutralizing properties B. Envelope proteins vary their antigenic structure C. Envelope proteins have low immunogenicity D. Envelope proteins are lost after recurrent replications E. Envelope proteins are sequestered within the hepatocytes

*The answer is E.* This case involves infection with either influenza A or influenza B virus, since both are circulating in the area. Of the drugs listed, only oseltamivir can be used for either influenza A or B. Zanamivir along with oseltamivir are neuraminidase inhibitors which block the release of the virus from infected cells. Amantadine and rimantadine block the release of the influenza A nucleic acid from the nucleocapsid, thereby preventing viral replication. These two drugs have no effect on the replication of influenza B viruses. Foscarnet is used for cytomegalovirus infections; ribavirin is used in combination therapy for hepatitis C virus; and ritonavir is a protease inhibitor used against HIV.

A 28-year-old man was clinically diagnosed with the flu after presenting to his physician with a fever of 102 °F, severe myalgia, fatigue, and rhinorrhea of 12 h duration. The physician had read local health department reports that said both AH1N1 and B viruses were circulating in the area. Which medication did she most likely prescribe? (A) Amantadine (B) Foscarnet (C) Ribavirin (D) Ritonavir (E) Zanamivir

*The answer is D.* Although all the immune mechanisms listed can play a role in defense against viruses, viral neutralizing antibodies are the most important defense mechanism against reinfection. Natural killer cells and interferon-α are important innate defenses which come into play following viral infections. Naïve, viral-specific cytotoxic T cells must be activated, but play an essential role in recovery from viral infections. Activated macrophages can phagocytize viral particles, secrete proinflammatory cytokines, and kill viral-infected cells, but do not play a role in prevention of infection.

A 3-year-old child presents with a 3-day history of cough, a profusely runny nose, and conjunctivitis, and a 1-day history of 40°C fever, and a blotchy, erythematous, maculopapular rash that began on his face and is now appearing on his chest. The child is toxic appearing. His history is significant for a lack of most childhood vaccines due to family religious beliefs. The child in the above case recovered uneventfully, was re-exposed to the same agent a year later, but did not become ill. What prevented the child from becoming infected on subsequent encounter with the agent? (A) Activated macrophages (B) Interferon-α (C) Naïve cytotoxic T cells specific for the agent (D) Neutralizing IgG antibodies specific for the agent (E) NK cells

*The answer is B.* The symptoms, including the prodromal signs, fever, and rash are typical of measles virus infection. In addition, the lack of vaccination supports this suggestion. The signs and symptoms described are not consistent with any of the other choices. Mumps typically presents as parotitis. Echoviruses can cause a mild summer rash illness.Rubella, also rare in the United States due to vaccination, is generally a mild illness with low-grade fever. The rash in varicella is itchy and consists of maculopapular eruptions, vesicles, and scabs, accompanied by a low-grade fever.

A 3-year-old child presents with a 3-day history of cough, a profusely runny nose, and conjunctivitis, and a 1-day history of 40°C fever, and a blotchy, erythematous, maculopapular rash that began on his face and is now appearing on his chest. The child is toxic appearing. His history is significant for a lack of most childhood vaccines due to family religious beliefs. Which is the most likely diagnosis? (A) Echovirus summer rash (B) Measles (C) Mumps (D) Rubella (E) Varicella

*The answer is C.* The patient has pertussis, which is characterized by a persistant cough. This can be prevented through vaccination.

A 3-year-old girl is brought to the emergency department by her father because of a persistent cough for 2 weeks. She sometimes vomits following a paroxysm of coughing. While she is not coughing, she appears well. She has not yet received any routine childhood vaccinations. Her temperature is 37°C (98.6°F). Physical examination shows petechiae over the sclera and face. Which of the following is the most likely diagnosis? (A) Diphtheria (B) Influenza (C) Pertussis (D) Plague (E) Tularemia

*The answer is C.* A member of the lentivirus subgroup of retroviruses, the human immunodeficiency virus (HIV) has a diploid genome that consists of single-stranded, positive-sense RNA. The HIV-1 provirus (ie, the latent form of the virus that is integrated into the host cell DNA) contains three structural genes (gag, pol, and env) and six regulatory genes (tat rev, vif, vpr, nef and vpu). While the tat and rev genes are required for replication, the vif, vpr, ne and vpu genes are not necessary for replication and are considered accessory genes. The structural genes code for polyprotein precursors that contribute to virion assembly. More specifically, the gag gene encodes group-specific antigens in the virion core such as nucleocapsid proteins p24 and p1, pol encodes several proteins such as reverse transcriptase, and the env gene indirectly encodes the envelope glycoproteins gp120 and gp41.

A 32-year-old male presents to the emergency department with progressive fatigue malaise and lymphadenopathy. When tested for HIV infection, his blood samples are positive for viral protein p24. The protein detected in this patient is a product of which of the following viral genes? A. pol B. env C. gag D. nef E. rev F. tat

*The answer is A.* The pathogen responsible for hepatitis A is an RNA picornavirus with an average incubation period of 30 days. Transmission occurs through the fecal-oral route and is common in areas with overcrowding and poor sanitation. Outbreaks frequently result from contaminated water or food with raw or steamed shellfish the typical culprit in the United States. Onset is acute, and symptoms can include malaise, fatigue, anorexia, nausea, vomiting, mild abdominal pain, and an aversion to smoking. Hepatomegaly is commonly seen. AST and ALT spike early in the illness, followed by increases in bilirubin and alkaline phosphatase. Anti-HAV IgM is positive on the hepatitis panel. Fortunately, hepatitis A infection is a self-limiting disease and does not progress to chronic hepatitis, cirrhosis, or hepatocellular carcinoma. The mortality rate is less than 0.2%, although a significantly prolonged prothrombin time correlates with increased mortality. Treatment of hepatitis A infection is largely supportive, with complete recovers/expected in 3-6 weeks. Close contacts of individuals with hepatitis A should promptly be given immune globulin. People considered at high risk (eg, those living in or traveling to endemic areas, those with chronic liver disease or clotting-factor disorders, men who have sex with men) should be given the hepatitis A vaccine as prophylaxis.

A 34-year-old Caucasian nurse with recent onset of malaise is found to have the following set of laboratory findings: This patient most likely: A. Had oysters at a local restaurant B. Consumed boiled eggs C. Had a recent tattoo D. Had an accidental needlestick E. Had an unprotected sexual intercourse

*The answer is A.* Although all the diseases listed are tickborne, Colorado tick fever (CTF) and tick-borne encephalitis are the only ones caused by a virus. Tickborne encephalitis occurs in Europe and Russia. Lyme disease, caused by the bacterium Borrelia burgdorferi, typically occurs in the northeast and northern Midwest and presents with a rash and arthritis. Tickborne relapsing fever, caused by Borrelia hermsii, is found in coniferous forests of the western United States and Canada. It can present as recurring episodes of fever along with a variety of nonspecific symptoms including headache, myalgia, and arthralgia. Rocky Mountain spotted fever is caused by Rickettsia rickettsii. This disease was first described in the Rocky Mountain area; however, the majority of cases occur in North and South Carolina, Missouri, Arkansas, and Oklahoma.

A 34-year-old man, an avid hiker from New Jersey, presents with a fever, fatigue, headache, malaise, myalgia, and arthralgia. The patient reported that the fever had first occurred 1 week ago and lasted for 3 days, then resolved for 3 days, and returned, at which time he sought medical attention. His history is significant for a recent hiking trip in Utah during which he experienced a tick bite. Which tick-borne viral disease might this man have contracted in his hiking trip? (A) Colorado tick fever (B) Lyme disease (C) Relapsing fever (D) Rocky Mountain spotted fever (E) Tick-borne encephalitis

*The answer is E.* The term arbovirus is used for those viruses transmitted by arthropods, such as mosquitoes or ticks. Yellow fever virus, a mosquito-borne virus, is endemic in South America and Africa. This is the only arbovirus for which a human vaccine is available. Vaccination against Yellow fever is recommended for travelers to endemic areas. Arenaviruses are not transmitted by arthropods, therefore are not arboviruses. Although this woman will be at risk for dengue virus, Venezuelan equine encephalitis virus, and possibly West Nile virus, there are no human vaccines routinely available for these agents.

A 36-year-old woman is preparing for an adventure trip down the Amazon River in Brazil by receiving recommended vaccinations. Against which arbovirus should she be vaccinated? (A) Arenavirus (B) Dengue virus (C) Venezuelan equine encephalitis virus (D) West Nile virus (E) Yellow fever virus

*The answer is D.* Rubeola is caused by infection with the measles virus a member of the paramyxovirus family. The measles virus is an enveloped, non-segmented, negative-sense RNA virus. A classic clinical manifestation of measles is the presence of numerous small blue-white spots on the buccal mucosa adjacent to the second molars ("Koplik spots"). The Koplik spots are sometimes likened to "grains of sand" on an erythematous base. When Koplik spots are accompanied by cough, coryza, and conjunctivitis measles infection is the likely diagnosis. In fact a mnemonic for the initial clinical presentation of typical measles is "CCCK" (cough, coryza, and conjunctivitis and Koplik spots). In typical measles the appearance of "CCCK"heralds the development of a cutaneous maculopapular rash with in the next day or two. This patient's recent immigration status also supports a diagnosis of measles as he may not have been vaccinated against measles mumps and rubella (MMR) at 12-15 months of age.

A 4-year-old Asian immigrant is brought to clinic with high fever nasal discharge lacrimation and dry cough. Physical examination reveals several blue-white spots on his buccal mucosa. Over the next several days, which of the following is most likely to develop? A. Bronchiolitis B. Parotitis C. Profuse diarrhea D. Skin rash E. Jaundice

*The answer is B.* This case is descriptive of myocarditis. This inflammatory condition can result from infectious or noninfectious causes. Viruses are the most common cause of myocarditis when a cause can be identified. The fact that the virus was identified using reverse transcriptase PCR indicates that the viral genome is RNA. Of the viruses, coxsackie B viruses are most frequently involved. These RNA viruses are members of the enterovirus group of the family Picornaviridae. Influenza virus and measles virus are also RNA viruses; however, they are rarely involved in viral myocarditis. Adenovirus, particularly serotypes 2 and 5 are important causes of myocarditis; however, they are DNA viruses. Cases of parvovirus B19 associated myocarditis have been reported; however, it too is a DNA virus and thus not the etiologic agent of this case.

A 43-year-old man is hospitalized after presenting to the emergency department with fever, chest pain, and shortness of breath after mild exertion. Physical exam reveals tachycardia out of proportion with his fever. He reports a flulike illness 2 weeks previously. A biopsy, taken after the patient began to show signs of heart failure, reveals mononuclear infiltration in the myocardial tissue. Reverse transcriptase PCR identified a viral cause. What is the most likely etiological agent causing this man's condition? (A) Adenovirus type 7 (B) Coxsackievirus B (C) Influenza virus (D) Measles virus (E) Parvovirus B19

*The answer is D.* The symptoms are most consistent with West Nile neurologic disease, a rare complication of West Nile virus infections.

A 64-year-old man living on a farm in southern Minnesota is brought on July 15 to the emergency room by his brother. The brother said the man had a 2-day history of fever, headache, and some vomiting, but today he appeared confused. He is confused by some of the simple questions you ask him. His spinal tap is clear with 75% PMNs and a head CT is normal. The most likely cause of his symptoms is (A) California encephalitis virus (B) Enterovirus (C) HSV (D) West Nile virus

*The answer is D.* Influenza viruses are noted for their high degree of antigenic variation, arising from point mutations in the genes for the envelope glycoproteins hemagglutinin (HA) and neuraminidase (NA). This type of antigenic variation in influenza viruses is called antigenic drift, and occurs in both group A and group B viruses. As the viruses circulate around the world each year, isolates are antigenically typed and the predicted predominant serotypes of H1N1, H3N2, and B virus are propagated and incorporated into vaccines. New vaccines are made each year due to differences in predominant serotypes from one year to the next. Reassortment of RNA strands between animal and human strains is an example of another, fortunately rare type of antigenic change that occurs in influenza A viruses. Influenza A viruses can infect several different species of animals, whereas influenza B viruses are species specific. If an animal gets infected with two different influenza A viruses, the eight separate strands of RNA that make up the genome of each virus can be combined such that virions emerge from the infected cell containing RNA strands from both viruses and representing a new influenza A subtype. This process is called antigenic shift. Subtypes of influenza A, including those currently in circulation (A/H1N1 and A/H3N2) have emerged by antigenic shift and have caused pandemics leading to the death of hundreds of millions of people. Because antigenic shift is an infrequent event, it does not contribute to the need for annual vaccination. Worldwide surveillance to detect the emergence of new influenza A viruses by antigenic shift or other mechanisms is an important function of the World Health Organization, the Centers for Disease Control and Prevention, and similar organizations around the world. Influenza viruses do not acquire genes from parainfluenza viruses, nor does antigenic variation occur in the matrix protein. The HA protein contains a segment called a fusion peptide, but its level of expression does not change.

A 65-year-old woman refuses to be vaccinated against influenza virus because she was vaccinated the previous year. What changes in the virus necessitate annual vaccination? (A) Acquisition of new genes through coinfection of cells with parainfluenza viruses (B) Antigenic changes in the viral matrix protein (C) Changes in the level of expression of the envelope fusion proteins (D) Mutations in the genes for the envelope glycoproteins (E) Reassortment of RNA strands between animal and human strains

*The answer is C.* Because the incubation period of rabies is usually long (more than 2 weeks—unless bitten on the face) and the disease is completely preventable with neutralizing antibodies, vaccination is used to generate those antibodies. The first dose of rabies prophylaxis consists of both the immune globulin for immediate protection and active rabies vaccine to promote the generation of neutralizing antibodies. Four additional doses of the active vaccine are given at least 1 week apart. Rabies prophylaxis is given to prevent disease in the exposed individual; it is not given to prevent spread of the virus from the exposed individual. The vaccine is not administered along with interferon. There is no antiviral therapy for rabies.

A 66-year-old man was bitten on the right index finger by a bat while in his bed. He washed the wound but did not seek medical care for the bite. Five weeks later, he went to the emergency room complaining of headache, malaise, drowsiness, pain, and weakness in his right hand. From his history of the bat bite, he was immediately treated with rabies prophylaxis. What was he given? (A) Interferon-α plus rabies immune globulin (B) Rabies immune globulin (C) Rabies immune globulin plus rabies vaccine (D) Rabies vaccine plus interferon-α (E) Ribavirin plus interferon-α

*The answer is D.* Because the incubation period of rabies is usually long (more than 2 weeks—unless bitten on the face) and the disease is completely preventable with neutralizing antibodies, vaccination is used to generate those antibodies. The first dose of rabies prophylaxis consists of both the immune globulin for immediate protection and active rabies vaccine to promote the generation of neutralizing antibodies. Four additional doses of the active vaccine are given at least 1 week apart. Rabies prophylaxis is given to prevent disease in the exposed individual; it is not given to prevent spread of the virus from the exposed individual. The vaccine is not administered along with interferon. There is no antiviral therapy for rabies.

A 66-year-old man was bitten on the right index finger by a bat while in his bed. He washed the wound but did not seek medical care for the bite. Five weeks later, he went to the emergency room complaining of headache, malaise, drowsiness, pain, and weakness in his right hand. From his history of the bat bite, he was immediately treated with rabies prophylaxis. Why was the man given rabies prophylaxis? (A) Interferon enhances the efficacy of rabies vaccine (B) Prophylaxis with antiviral drugs and interferon blocks viral replication (C) Rabies prophylaxis reduces the person-to-person spread of rabies (D) The immune globulin provides immediate but short-lived protection and the vaccine generates long-lasting neutralizing antibodies (E) The vaccine generates antibody directed against host viral receptors preventing migration of rabies virus into the CNS

*The answer is E.* Prior to the introduction of West Nile virus (WNV) into the United States in 1999, St Louis encephalitis virus was the most common arbovirus in the United States. WNV entered the United States in New York City, causing 66 cases in 1999. It spread rapidly across the United States, causing an average of 3,000 cases every year since its introduction (range of 21 cases in 2000 to 9,862 cases in 2003). Very few cases of arbovirus encephalitis other than that attributable to WNV occur annually in the United States.

A 67-year-old male in Minnesota is hospitalized in August with fever, lethargy, and disorientation. Cerebral spinal fluid analysis reveals a WBC count of 100 with 65% mononuclear cells, elevated protein, and normal glucose. IgM antibodies to the most common arbovirus in the United States are found in his serum. With which virus is he infected? (A) Eastern equine encephalitis virus (B) LaCrosse virus (C) St Louis encephalitis virus (D) Western equine encephalitis virus (E) West Nile virus

*The answer is D. All the viruses listed can cause pneumonia; however, by far, the most common cause of pneumonia in children less than 1 year of age is respiratory syncytial virus.

A 9-month-old child is hospitalized with viral pneumonia. Which virus is the most likely cause? (A) Adenovirus (B) Influenza virus (C) Parainfluenza virus (D) Respiratory syncytial virus (E) Varicella-zoster virus

*The answer is D.* RSV has F and G glycoproteins. The G protein is involved in attachment and F protein induces the fusion of the viral envelope with the host cell surface to facilitate entry.

A child who was complaining of sore throat and breathing problems was tested for the presence of antibodies to several of the common respiratory viral pathogens. Laboratory tests of the patient's serum revealed the presence of anti-G and anti-F antibodies. Which virus do you suspect as the etiologic agent of this child's illness? A) Adenovirus B) Influenza virus C) Herpesvirus D) RSV E) Parainfluenza virus

*The answer is C.* Although many of the childhood vaccines like measles, mumps, and chickenpox contain live, attenuated virus, the Salk poliovirus vaccine contains killed virus.

A killed virus vaccine is (A) Jeryl Lynn mumps vaccine (B) Enders measles vaccine (C) Salk poliovirus vaccine (D) Oka varicella-zoster vaccine

*The answer is C.* This infant presents with thrush and chronic diarrhea, which are suggestive of neonatal HIV infection in the context of the mother's social history. Zidovudine (ZDT, formerly AZT) is the prototype nucleoside reverse transcriptase inhibitor used in maternal HIV prophylaxis during pregnancy. HIV presents in the neonate with recurrent infection, recurrent diarrhea, and leukopenia. According to the CDC, in the United States, without antiretroviral therapy, approximately 25% of pregnant women infected with HIV will transmit the virus to their child. Since the advent of maternal antiretroviral therapy in 1992, there has been a >96% reduction in new cases of perinatal AIDS, now at about 50 cases annually, and fewer than 300 annual perinatal HIV transmissions. ZDT prophylaxis should continue in the neonate following birth for 6 weeks.

A newborn male presents to the emergency room with a fever and the oropharyngeal findings shown in Figure A. The patient's mother reports that he also has chronic diarrhea, and laboratory workup shows lymphocytopenia. During a careful review of the social history, you learn that the mother has a history of IV drug abuse and commercial sex work. She was prescribed prenatal medications, but failed to take one of them as directed. Which of the following may have helped prevent this patient's condition? A. Folic acid B. Acyclovir C. Zidovudine D. Ribavirin E. Zanamivir

*The answer is A.* Equine encephalitis virus is transmitted among the bird reservoir by mosquitoes. Transmission of the virus to humans typically occurs in the late summer or early fall after a large number of birds and mosquitoes have become infected. Although horses can be sickened by this virus, they do not develop a sufficient level of viremia necessary to infect another mosquito. The same is true for humans; thus, horses and humans are considered "dead-end hosts" for the virus. Of the mammals listed, only rodents such as the rat serve as reservoirs for arboviral encephalitides (i.e., the California group viruses such as LaCrosse virus) Fleas serve as vectors for Yersinia pestis, the causative agent of the plague. In the United States, ticks serve as vectors for the bacteria causing Lyme disease, Rocky Mountain spotted fever, and ehrlichiosis, and the virus causing Colorado tick fever. Ticks transmit encephalitic viruses in Europe, Russia, and 4other areas of the world.

A previously healthy 56-year-old woman in Florida dies of eastern equine encephalitis virus. Viral activity had been detected at that time by the local health department in which reservoir and vector species, respectively? (A) Birds; mosquitoes (B) Cattle; soft bodied ticks (C) Foxes; hard bodies ticks (D) Horses; mosquitoes (E) Rats; fleas

*The answer is B.* Coinfection by segmented viruses such as influenza can result in the exchange of segments from different serotypes to produce new serotypes (H1N2 & H2N1). This process is termed reassortment. Reassortment refers to the exchange of segmented genomes of different viral serotypes and/or recombination of genes on different segments. This is common in influenza, whose segmented genome is composed of 8 different segments. Hemagglutinin and neuraminidase are located on different segments; therefore, when two different serotypes coinfect a cell, there exists the possibilty of reassortment and the creation of a new serotype.

A scientist performed an experiment to produce hybrid viruses by mixing two different serotypes of influenza virus, H1N1 and H2N2, in a respiratory epithelium cell line. Several days later, the scientist collected the media and analyzed the viral progeny. She found the following serotypes of virus: H1N1, H2N2, H1N2, and H2N1. Which of the following terms best explains the appearance of new serotypes? A. Recombination B. Reassortment C. Complementation D. Phenotypic mixing E. Transformation

*The answer is E.* Because hepatitis A virus (HAV) is transmitted through the fecal-oral route, improved sanitary conditions (frequent hand-washing, appropriate food heating, and the avoidance of food and water in endemic areas) serve to limit outbreaks of infection. When HAV contamination is a concern, the virus can be inactivated with water chlorination, bleach (1:100 dilutions) formalin, ultraviolet irradiation, or boiling to 85°C for one minute.

A small outbreak of hepatitis A infection is reported by epidemiological services. Which of the following treatments is most likely to destroy the virus in the contaminated products? A. Drying B. Treating with 20% diethyl ether C. Treating with acid (pH = 1.0) D. Heating to 60°C for an hour E. Boiling for 1 minute

*The answer is E.* All viral replication requires transcription of viral specific mRNA directly or indirectly from the viral genome. The transcription allows viral proteins to be synthesized by the host cell ribosomal machinery for translation. This question describes a specific situation in which the viral specific mRNA is polycistronic (meaning it contains multiple cistrons, or genes, within the same mRNA transcript) and produces a polyprotein product or functional individual viral proteins to be generated, the polyprotein product must be cleaved by a specific viral protease. The viruses that demonstrate this particular method of viral replication include the single-stranded, positive-sense, linear, nonsegmented RNA viruses. A SS+ virus has a genome that is independently infective if transferred into a host cell and that functions as its own mRNA. Among the viruses listed, only echovirus possesses an 33+ RNA genome.

A virus-encoded polypeptide detected in infected human cells has a specific protease activity essential for generating several functional viral proteins from a large precursor polypeptide. Which of the following viruses is most likely studied in the experiment? A. Measles virus B. Rabies virus C. Influenza virus type A D. Rotavirus E. Echovirus

*The answer is A.* A major determinant of viral tropism for the specific tissues of specific hosts is the extent to which the viral surface proteins can bind to complementary host cell plasmalemma receptors. In the case of an enveloped virus, whether or not the virus can attach to a specific host cell generally depends on if a viral envelope glycoprotein with a high binding affinity for a host cell surface glycoprotein is present. A mutation in a viral-encoded envelope glycoprotein can therefore dramatically affect the range of host cells that the virus can attach to or infect. One such example would be a mutation in the hemagglutinin of an influenza A strain that was previously confined to domestic livestock. If the mutation conferred a new binding affinity for a neuraminic acid-containing glycoprotein on the surface of human nasopharyngeal epithelial cells, then the virus would no longer be threat only to domestic livestock and humans would be vulnerable to infection.

After exposure to mutagens, several strains of enveloped RNA viruses isolated from the nasal exudate of experimental animals acquire the ability to infect human epithelial cells. Which of the following viral-encoded proteins is most likely to have mutated in this circumstance? A. Surface glycoprotein B. Capsid protein C. RNA polymerase D. Endonuclease E. Protease

*The answer is B.* Amantadine binds to the M2 protein of influenza A virus, which inhibits this ion pore and prevents uncoating of the virus.

Amantadine inhibits (A) Influenza A and B virus hemagglutinin binding activity (B) Influenza A virus M2 protein activity (C) Influenza A and B virus neuraminidase activity (D) Influenza B virus RNA-dependent RNA polymerase activity

*The answer is E.* Influenza virus A attaches to the host respiratory epithelium cell and is subsequently endocytosed into the cell. In order for viral replication to occur, the viral genome must be released from the surrounding protein coat or capsid. The viral envelope protein M2 serves to translocate hydrogen ions from the endosome into the internal compartment of the virus. This maneuver facilitates the fusion of the viral envelope with the endosomal membrane, thereby releasing the viral RNA from the capsid in a process called uncoating. Amantadine and a related compound, rimantadine, block the activity of the M2 protein. Resistant strains of influenza A have been found to have single amino acid substitutions at four sites in the M2 protein.

Amantadine is a drug used to reduce the ill effects of an influenza virus A infection; however, increasing levels of resistance have limited its usefulness. Resistant strains of influenza A contain single amino acid substitutions in the M2 protein. With which aspect of the virus replication cycle is this protein involved? (A) Attachment (B) Genome replication (C) Penetration (D) Release (E) Uncoating

*The answer is B.* This child initially presented with fever, rhinitis, and pharyngitis, symptoms of an upper respiratory tract infection (URI). Most URIs (with or without pharyngitis) are caused by viruses, with roughly 15-20% of childhood cases of pharyngitis and 5-10% of adulthood cases of pharyngitis caused by bacteria. When a URI-stricken child such as this one develops a brassy cough and breathing difficulties, it is likely he has developed acute laryngotracheobronchitis (croup). The dyspnea associated with croup occurs when inflamed subglottic tissue obstructs the upper airway, and the characteristic stridor of croup is a sign that the URI has spread to include the larynx. Croup is typically caused by the standard URI viruses with the parainfluenza viruses (members of Paramyxoviridae) most commonly =responsible.

An 18-month-old male is seen on an outpatient basis for fever, runny nose, and sore throat. Two days later, he is brought to the emergency department with persistent fever, brassy cough and difficult breathing. Physical examination reveals stridor. Which of the following pathogens is most likely responsible for this patient's condition? A. Rhinovirus B. Paramyxovirus C. Togavirus D. Parvovirus E. Calicivirus

*The answer is B.* This patient has Respiratory syncytial virus.

An 8-month-old girl is brought to the emergency department because of a 1-day history of rapid breathing. Her temperature is 38.4°C (101.1°F), pulse is 160/min, respirations are 60/min, and blood pressure is 100/68 mm Hg. Bilateral expiratory wheezing and crackles are heard on auscultation. A chest x-ray shows areas of atelectasis and hyperinflation. Which of the following is the most likely causal virus? (A) Measles virus (B) Respiratory syncytial virus (C) Rhinovirus (D) Rotavirus (E) Varicella-zoster virus

*The answer is B.* Many recent immigrants to the United States will not have completed the CDC recommended vaccination regimen at the appropriate intervals. It is quite likely then that this patient was not vaccinated against measles, mumps, and rubella (MMR) at age 12-15 months. Among the acute viral exanthems, measles (rubeola) and German measles (rubella) are characterized by a maculopapular rash that begins on the face and spreads to include the trunk and extremities. Postauricular and occipital lymphadenopathy is particularly common in rubella, which is caused by a togavirus. Rubeola, in contrast, is caused by a paramyxovirus.

An 8-year-old Middle Eastern immigrant is brought to clinic with low-grade fever and a skin rash that started on his face and spread down his body. Physical examination reveals post-auricular tenderness. Which of the following is the most likely cause of this patient's disease? A. Herpesvirus B. Togavirus C. Reovirus D. Paramyxovirus E. Parvovirus

*The answer is A.* The congenital rubella syndrome is predominantly characterized by neonatal defects of the head (microcephaly, mental retardation), eyes (cataracts), ears (deafness), and heart cardiovascular system (patent ductus arteriosus, peripheral pulmonicmstenosis). The most classic clinical triad of congenital rubella includes congenital cataracts (white pupils) sensory-neural deafness, and patent ductus arteriosus. Live attenuated rubella virus vaccine is currently recommended not only for children at 12-15 months and again at-6 years of age but also in non-pregnant women of childbearing age who lack serum antibody against rubella. At the time of vaccination women are strongly advised to avoid pregnancy for the next four weeks. This vaccination policy has markedly decreased the incidence of congenital rubella.

An infant born to a 27-year-old immigrant is evaluated for hearing loss. Physical examination demonstrates white pupils and a continuous machinery murmur over the left infraclavicular area. Which of the following prenatal interventions would have most likely prevented this infant's condition? A. Live attenuated vaccine B. Viral component vaccine C. Killed vaccine D. Toxoid vaccine E. Viral enzyme inhibitor drug F. Cellular receptor inhibitor drug G. Interferons H. Prenatal vitamins

*The answer is B.* Respiratory syncytial virus (RSV) is a paramyxovirus. The envelope proteins of this virus involved in attachment and entry into the cell are the G protein and the fusion protein, respectively. The G protein attaches to the receptor on the host cell membrane and the fusion protein mediates the fusion of the viral envelope with the cell's plasma membrane, delivering the nucleocapsid directly into the cytoplasm. Palivizumab is a humanized monoclonal antibody directed against the fusion protein. It is used as prophylaxis in infants born during the RSV season (winter to spring), who are at high risk of lower respiratory tract disease due to RSV. Infants at highest risk include premature infants and infants born with cardiopulmonary disease. RSV does have capsid and matrix proteins; however, unlike the closely related parainfluenza viruses, it lacks hemagglutinin-neuraminidase protein.

An infant is born prematurely in February. Concerned about the risk of serious infection with respiratory syncytial virus, he is treated with the monoclonal antibody palivizumab before being released from the hospital. What is the viral target of this monoclonal antibody? (A) Capsid protein (B) Fusion protein (C) Hemagglutinin protein (D) Neuraminidase protein (E) Matrix protein

*The answer is D.* Rabies virus is usually transmitted via the bite of an infected animal, and the woman's symptoms are consistent with those of rabies. California encephalitis virus, transmitted by arthropods, causes meningitis and encephalitis. Hantaan virus is transmitted through aerosols formed from dried rodent excretions. This virus causes hemorrhagic fever and severe pulmonary infections. Ebola virus can be transmitted by an animal, but infection causes severe hemorrhagic fever. Lymphocytic choriomeningitis virus is a cause of viral meningitis and a relatively benign infection with little mortality. Humans are infected by inhaling contaminated aerosols, by eating food containing viral particles, or by exposure of open wounds to infected soil.

An ornithologist was on a 3-month trip to study several species of birds living in a rain forest in South America. On the 10th day of her trip, she was bitten on the hand by an unusually aggressive bat. The scientist applied a topical antibiotic ointment and continued her research. Four weeks later, the scientist lost feeling in her hand. She shortly began experiencing high fever, periods of rigidity, difficulty in swallowing liquids, drooling, and disorientation. Death followed rapidly. A postmortem biopsy of her brain showed the presence of Negri bodies. These symptoms are consistent with: A. California encephalitis virus. B. Hantaan virus. C. Ebola virus. D. rabies virus. E. lymphocytic choriomeningitis virus.

*The answer is D.* The human Calicivirus, better known as Norwalk virus, is an important cause of viral gastroenteritis, tends to occur in outbreak fashion, and can cause infection with as few as 10 virus particles. Caliciviruses are nonenveloped viruses and are thus more resistant to environmental conditions than are viruses surrounded by a lipid envelope. Caliciviruses are resistant to desiccation and to levels of chlorine as high as 10 ppm. Immunity is short-lived and there is no vaccine. Outbreaks of Norwalk virus are associated most commonly with ingestion of contaminated food. Person-to-person transmission through a fecal-oral route or infection via contaminated fomites also leads to outbreaks. The virus can become aerosolized from fecal material or vomitus, and infection can occur following such exposure, but this route of transmission is not common.

An outbreak of Calicivirus occurs in a home for disabled adults. What is an important characteristic of this virus group that influences the occurrence of disease outbreaks and their control and prevention? (A) Long-term immunity after infection or vaccination (B) Low infectious dose required for infection (C) Susceptibility of the virus to chlorine cleaning agents (D) Susceptibility of the virus to desiccation (E) Transmission by inhalation of aerosolized virus particles

*The answer is B.* Ebola virus has one of the highest mortality rates of any viral disease affecting humans. The clinical manifestations described are typical for Ebola virus. Outbreaks of this viral infection occur periodically in sub-Saharan Africa, and typically spread from the index patient to the care givers through contact with blood and body fluids. Dengue virus, Yellow fever virus, and West Nile virus are transmitted by mosquitoes, and, although they cause serious morbidity, their mortality rate is much lower than that of Ebola virus. Hantavirus pulmonary syndrome occurs in the Americas, is transmitted by inhalation of virus in rodent urine and feces, and is not transmitted person-to-person.

An outbreak of a hemorrhagic virus occurs in a village in Uganda, Africa. Clinical manifestations included hemoptysis, bleeding from the eyes, skin, and gastrointestinal tract. The mortality rate exceeded 70%. The virus appeared to be transmitted in the village by contact with the blood and bodily secretions of affected individuals; thus, infection rates were highest among those caring for the sick. Which viral disease was involved in this outbreak? (A) Dengue hemorrhagic fever (B) Ebola (C) Hantavirus pulmonary syndrome (D) West Nile fever (E) Yellow fever

*The answer is A.* NNTIs bind to reverse transcriptase, inhibiting the enzyme.

During an experimental study, an investigator develops a new member of the class of non-nucleoside reverse transcriptase inhibitors. This new drug most likely inhibits HIV infection through which of the following mechanisms? (A) Binding to reverse transcriptase (B) Binding to RNase H (C) Blockade of integration (D) Incorporation into viral DNA (E) Phosphorylation of nucleoside trisphosphates

*The answer is A.* This patient's immigration history suggests that she may not have been vaccinated against measles, mumps, and rubella (MMR) at 12-15 months of age. Measles (rubeola) and German measles (rubella) are two acute viral exanthems whose maculopapular rashes begin on the head and neck and spread downward. Generalized lymphadenopathy, particularly postauricular and occipital, is typically more prominent in rubella. Most adult women with rubella develop polyarthritis and polyarthralgia as sequelae. Fetal infection with the rubella virus during the first trimester can cause sensory neural deafness cataracts and cardiac malformations like a patent ductus arteriosus. Maternal deafness, meningitis, or pneumonia would be yew unlikely.

During the first trimester of pregnancy a 22-year-old immigrant from the Middle East develops a low-grade fever and maculopapular rash. Over 48 hours the rash spreads from her face and chest to her trunk and extremities. Physical .examination also detects post auricular lymphadenopathy. The mother is at risk for which of the following immediate complications (from the first column) and the fetus is at risk for which of the following congenital defects (from the second column)?

*The answer is B.* Oseltamivir (Tamiflu) is a neuraminidase inhibitor. Neuraminidase is an enzyme which functions to cleave sialic acid, a monosaccharide derivative common on host cells and serving as a component of many surface receptors. In the case of influenza virus, sialic acid serves as the viral receptor.

In January, a 66-year-old woman presents a fever of 102 °F, chills, back pain, headache, and marked fatigue. Her physician prescribes oseltamivir and she rapidly recovers. With which etiologic agent was she infected? (A) Coronavirus (B) Influenzavirus (C) Parainfl uenza virus (D) Respiratory syncytial virus (E) Varicella-zoster virus

*The answer is A.* This case is descriptive of dengue hemorrhagic fever. The high fever, severe body aches and petechiae are typical for this viral disease. Hemorrhagic manifestations usually appear after the fever has spiked and returned to normal. A positive tourniquet test demonstrates the formation of at least 20 petechiae per square inch on the skin of the arm elicited by inflating a blood pressure cuff on the upper arm for 5 min. This test is one of the criteria for clinical diagnosis of dengue hemorrhagic fever. Dengue virus is endemic in most tropical and subtropical areas around the world and a few cases of dengue are reported almost every year among travelers returning to the United States from those areas. The outcome of infection with this virus ranges from asymptomatic infection to fever and severe body aches to hemorrhagic disease with or without shock. There are four strains of the virus, and infection with one strain does not protect against infection with the others. Indeed, reinfection with a second strain is associated with more severe disease including hemorrhage and shock, particularly in children. Ebola virus causes a highly fatal hemorrhagic fever and has only been found in sub-Saharan Africa. Epstein-Barr virus (EBV) typically causes low grade fever, pharyngitis, cervical lymphadenopathy, and profound fatigue. The white blood cell count in EBV-associated mononucleosis does show lymphocytosis as in the present case; however, atypical lymphocytes are usually more than 10%. Hepatitis A virus presents as an acute onset of abdominal pain with nausea and vomiting. Parvovirus B-19 is a mild rash illness most commonly seen in school-aged children.

Four days after returning to the United States from a trip to the Caribbean, a 34-year-old man presents with fever that had been as high as 39 °C two days previously but had returned to normal, severe headache, and severe pain behind the eyes, in the joints, and in the muscles. Physical exam reveals a macular rash seen on the trunk and extremities, hepatomegaly, petechiae on mucous membranes of the mouth and induced on the arm following a tourniquet test. Laboratory tests reveal a white blood cell count of 6,720 with 30% neutrophils, 50% lymphocytes, 16% monocytes, and 4% atypical lymphocytes and 65,000 platelets. IgM to which virus was found in his serum? (A) Dengue virus (B) Ebola virus (C) Epstein-Barr virus (D) Hepatitis A virus (E) Parvovirus B-19

*The answer is D.* Dengue virus is transmitted by mosquitoes of the genus Aedes. Two species of Aedes mosquitoes capable of serving as a vector for dengue virus are found in the southern United States, and have on occasion transmitted the virus from a returned traveler to people in the community. The virus is not transmitted in fecal contaminated water, thus avoiding places with poor public hygiene and drinking only bottled water when visiting endemic areas will not prevent infection with dengue virus. There is no prophylactic medication to prevent dengue, as there is to prevent malaria. No vaccine is available to prevent dengue.

Four days after returning to the United States from a trip to the Caribbean, a 34-year-old man presents with fever that had been as high as 39 °C two days previously but had returned to normal, severe headache, and severe pain behind the eyes, in the joints, and in the muscles. Physical exam reveals a macular rash seen on the trunk and extremities, hepatomegaly, petechiae on mucous membranes of the mouth and induced on the arm following a tourniquet test. Laboratory tests reveal a white blood cell count of 6,720 with 30% neutrophils, 50% lymphocytes, 16% monocytes, and 4% atypical lymphocytes and 65,000 platelets. Which method is best for prevention of this infection? (A) Avoiding places with poor public hygiene when visiting endemic areas (B) Drinking only bottled water (C) Taking prophylactic ribavirin (D) Use of insect repellent (E) Vaccination

*The answer is C.* A marked antigenic change in the N (neuraminidase) protein, the H (hemagglutinin) protein, or both is termed antigenic shift. In antigenic drift, there is also an antigenic change in one or both of these proteins, but the change is much less significant. With antigenic drift, although the H protein does change antigenically, H1 remains H1, for example.

From 1918 until 1956, the only subtype of influenza observed in humans was H1N1. In 1957, H1N1 was replaced by H2N2. This is an example of: A. viral interference. B. phenotypic mixing. C. antigenic shift. D. antigenic drift. E. viral transformation.

*The answer is E.* The severe acute respiratory syndrome (SARS) outbreak began in the Guangdong region of southern China where it killed over 300 people before it came to the attention of the World Health Organization. It was spread to other countries by infected persons traveling by air during the incubation period. The virus generally caused a high fever with chills, headache, malaise followed by severe respiratory signs including unproductive cough, hypoxia, and dyspnea. Neurologic disease was not typically associated with this disease. Bird flu, another viral disease originating in China in the late 1990s, is caused by a novel influenza A virus termed A/H5N1. This virus has caused a few hundred human cases so far with about a 60% mortality rate. Hantavirus pulmonary syndrome was first described in the 1993 in the Four Corners area of the western United States. It is a zoonotic infection caused by several strains of rodent Hantaviruses.

In 2003, a previously unknown viral disease arose in China and spread to five countries around the world, causing thousands of cases with about a 10% overall mortality rate. The disease was attributed to a novel Coronavirus. What human disease did this newly described Coronavirus cause? (A) Aseptic meningitis (B) Bird flu (C) Hantavirus pulmonary syndrome (D) Meningoencephalitis (E) Severe acute respiratory syndrome

*The answer is B.* Hepatitis C virus has six or more genotypes and multiple sub genotypes, as demonstrated by the genetic differences in the encoding of its two envelope glycoproteins. This genetic variation has led to the development of a hypervariable region of the envelope glycoprotein that is especially prone to frequent mutation. Moreover there is no proofreading 3' — 5' exonuclease activity built into the virion-encoded RNA polymerase. As a result, the IRNA polymerase makes many errors during replication, and several dozen subspecies of hepatitis C virus are typically present in the blood of an infected individual at any one time.

HCV strains isolated from a single individual demonstrate significant variability. This genetic instability of HCV is attributed in large part to its RNA-dependent RNA-polymerase, which lacks: A. Nucleotide specificity B. 3' — 5' exonuclease activity C. 5' — 3' exonuclease activity D. Ligase activity E. Glycosylase activity F. Primase activity

*The answer is C.* Genetic shift in the influenza A virus involves reassortment of genomic segments of the human strain with genomic segments of the animal (particularly avian) strain when both viruses coinfect pigs. The resulting new strain can cause a new influenzam pandemic if it demonstrates dramatically altered viral surface glycoproteins (eg, hemagglutinin). The key structural feature that enables influenza viruses to undergo such relatively rapid genetic shifts through reassortment is the segmented nature of their genomes. Members of another virus family with a segmented genome could also undergo such reassortment—as opposed to the less radical, slower genetic drift that occurs in all viral families via point mutations. Among the viruses listed above, only rotavirus also has a segmented genome.

Human influenza virus is known to participate in genetic reassortment when exposed to animal orthomyxoviruses. Which of the following viruses is most likely to undergo a similar process? A. Poliovirus B. Human papilloma virus C. Rotavirus D. Measles virus E. Hepatitis C virus

*The answer is E.* For a naked (nonenveloped) RNA molecule to induce viral protein synthesis in the host cell, it must act as mRNA capable of using the host's intracellular machinery for translation. In other words the RNA molecule must be single- stranded and positive sense (SS+). Among the viruses listed, only rhinovirus (a picornavirus) contains SS+ RNA. Generally speaking, only naked SS+ RNA molecules are infectious, whereas the naked single-stranded negative sense (SS—) RNA molecules and the naked double-stranded RNA molecules are not. Other nonenveloped RNA viruses include enteroviruses (eg, poliovirus, coxsackievirus, echovirus, hepatitis A virus), reoviruses (eg, rotavirus), and Norwalk virus.

Naked RNA molecules are isolated from viral particles in the nasal exudate of a 23-year-old male. After introduction into human cells, the naked RNA molecules induce viral protein synthesis and viral genome replication. The patient is most likely infected with: A. Influenza virus type A B. Respiratory syncytial virus C. Rotavirus D. HIV E. Rhinovirus

*The answer is C.* The reverse transcriptase of retroviruses makes a DNA copy of the genomic RNA. This DNA must be integrated into the host-cell DNA in the nucleus for the remaining steps in the replication process to occur.

Negri bodies are associated with (A) Cytomegalovirus infections (B) Herpes simplex virus infections (C) Rabies virus infections (D) Rubella virus infections

*The answer is B.* Oseltamivir (Tamiflu) is a neuraminidase inhibitor. Neuraminidase is an enzyme which functions to cleave sialic acid, a monosaccharide derivative common on host cells and serving as a component of many surface receptors. In the case of influenza virus, sialic acid serves as the viral receptor. In order for a successful viral replication cycle to occur, the new virion must bud from the surface of the infected cell. If the new virions encounter sialic acid in abundance, they will bind and not be released to infect naïve cells. In order to facilitate the release of new virions, neuraminidase on the surface of influenza virus cleaves the sialic acid. As for naïve cell infections, neuraminidase action allows for the bound virus to penetrate the cell and proceed with infection. Thus, oseltamivir operates to prevent the action of neuraminidase, thereby trapping the virus on the surface of the naïve or infected host cells. Therefore, oseltamivir does not directly prevent viral replication (choice A), uncoating (choice C), nuclear translocation (choice D), or bind to the viral polymerase (choice E).

What is the mechanism of action of oseltamivir? (A) Directly prevents replication of the viral genome (B) Prevents the release of mature virions from the infected host cell (C) Inhibits the uncoating of the virus (D) Inhibits the translocation of the viral genome to the nucleus (E) Binds directly to the virus RNA polymerase active site

*The answer is B.* This disease has been virtually eliminated from the United States by vaccination. Cases occasionally occur among unvaccinated immigrants. The photograph shows an infant with cataracts. While many signs and symptoms reflecting involvement of multiple organs are seen in this disease, the classic triad of congenital rubella syndrome (CRS) is cataracts, deafness, and patent ductus arteriosus. Postnatal rubella is a mild febrile rash illness that may present without a rash, and with arthralgia, particularly in adult women. Classic signs and symptoms of congenital cytomegalovirus infection include petechial rash, microcephaly, chorioretinitis, and sensorineural hearing loss. Symptomatic infection of the mother during pregnancy would most likely have been manifested as a mononucleosis-like syndrome. Congenital varicella usually manifests as limb deformities, and infection of the mother during pregnancy would have caused severe chickenpox with a heightened risk of varicella pneumonia. Neonatal enterovirus infection could present as poor feeding, irritability, and rapid breathing, consistent with cardiac problems; however, cataracts are not seen in this disease. Neonatal herpes most commonly manifests as vesicular lesions on the skin and mucous membranes and keratoconjunctivitis. Disseminated disease could present as irritability, poor feeding, and rapid breathing in addition to other manifestations. Symptomatic infection of the mother during pregnancy would have manifested as vesicular genital lesions.

The 6-week-old infant shown in the photograph is brought to the emergency department with poor feeding, irritability, and rapid breathing. Studies reveal hepatosplenomegaly, bilateral deafness, and patent ductus arteriosus. The infant's mother, an undocumented immigrant, reported experiencing fever and joint pain that lasted a few days during her second month of pregnancy. The maternal illness is determined to be related to the infant's condition. What is the most likely diagnosis for the infant? (A) Congenital cytomegalovirus (B) Congenital rubella syndrome (C) Congenital varicella (D) Neonatal enterovirus infection (E) Neonatal herpes

*The answer is B.* Inadequate rate of immunization is repsonsible for the re-emergence of measles in select communities on the West Coast.

The factor facilitating the re-emergence of measles in select communities on the West Coast is which of the following? A) governmental instability B) inadequate rate of immunization C) increased injection drug abuse D) microbial adaptation E) the spread of HIV infection

*The answer is D.* Rotaviruses infect and replicate in the gastrointestinal tract and typically affect infants and very young children. Although rotavirus infections are seen worldwide, significant mortality exists only in developing countries or in situations where good medical treatment (for example, fluid and electrolyte replacement), is not available.

The typical clinical syndrome associated with rotavirus infection is: A. acute gastroenteritis of young adults. B. acute bronchiolitis of infants. C. acute hepatitis. D. nausea, vomiting, and diarrhea in infants and young children. E. acute paralytic syndrome.

*The answer is E.* All of the enteroviruses can cause CNS disease. The enteroviruses are the major cause of aseptic meningitis. Rhinoviruses cause the common cold whereas the Caliciviruses cause gastrointestinal diseases. Hepatitis virus C causes hepatitis and cirrhosis. Flaviviruses cause encephalitis and hemorrhagic fever. While West Nile virus can cause meningitis, this manifestation is not typical of the entire Flavivirus group.

Which of the following groups RNA viruses are common causes of viral meningitis? A. Rhinoviruses B. Caliciviruses C. Hepatitis C virus D. Flaviviruses E. Enteroviruses

*The answer is E.* The RotaTeq vaccine was licensed in 2006 and is recommended for use in children, beginning at 2 months of age. It consists of the five most common strains of rotavirus recombined with a bovine strain of rotavirus. Vaccines are available for all other diseases listed, except mad cow disease. No other available vaccines are made by recombining human and animal strains of viruses.

Which vaccine is made from reassorted bovine and human viruses? (A) Hepatitis A vaccine (B) Infl uenza vaccine (C) Mad cow disease vaccine (D) Poliovirus vaccine (E) Rotavirus vaccine

*The answer is D.* The genetic material of poliovirus is single stranded RNA, which can be translated into a large polyprotein that is subsequently cleaved into the individual viral proteins.

Viruses whose genomes have a messenger (positive-sense) polarity are (A) Adenoviruses (B) Papovaviruses (C) Paramyxoviruses (D) Polioviruses

*The answer is A.* Polio virus is spread by a fecal-oral route. In the vast majority of infected individuals, the virus replicates asymptomatically in the intestinal tract and is shed in the feces. Paralytic polio occurs in less than 1% of infected individuals and results from a viremia that allows the virus access to the central nervous system (CNS). Vaccination with both the OPV and IPV results in the production of neutralizing IgG antibody that blocks viral entrance into the CNS, thereby protecting against paralytic disease. The IPV, given by injection, only stimulates systemic immunity. Thus, a vaccinated individual can still develop an asymptomatic intestinal infection with the wild-type virus and shed the virus in the feces to other susceptible individuals in the community. In contrast, the OPV is a live, attenuated vaccine which replicates in the intestine and stimulates both systemic and intestinal immunity. The advantage of the OPV in areas where poliovirus is endemic is that, by stimulating intestinal immunity, a vaccinated individual is not only protected from paralytic disease, but also from asymptomatic intestinal infection. The use of the OPV stops asymptomatic transmission of the virus in the community. The disadvantages of the OPV are that it can be shed in the feces and cause disease in susceptible immune compromised family members. More importantly, there is a small risk of vaccine-induced paralytic polio. Reduction of wild-type poliovirus transmission in the United States has been so dramatic since the development of OPV that the occurrence of poliomyelitis in recent years has been due to imported cases or OPV-associated cases. The use of IPV has replaced the use of OPV in countries free from wild-type poliovirus transmission such as the United States.

Why do polio eradication programs in developing countries utilize the oral polio vaccine (OPV) rather than the inactivated polio vaccine (IPV)? (A) Persons immunized with IPV can still become infected with and shed wild-type virus. (B) The vaccine strain of IPV can be shed from the feces and cause disease in susceptible individuals. (C) The IPV cannot be used in immune deficient patients. (D) The IPV does not contain all strains of poliovirus. (E) Vaccine-induced cases of paralytic polio have occurred with IPV.