Medically Important Viruses

MEDICAL 347

Section II • Microbiology

IMPORTANT STEPS IN VIRAL REPLICATION

Spread

Viruses are spread basically by the same mechanisms (e.g., respiratory droplets or sexually) as other pathogens.

Arthropod-borne viruses are referred to as arboviruses.

Most belong to 3 formal taxonomic groups

•Togavirus encephalitis viruses (a.k.a. alphaviruses)

•Flavivirus

•Bunyavirus

Vectors

•Mosquitoes are most common vectors.

•Ticks, biting midges, and sandflies are less common.

Attachment

Viruses bind through specific interaction with the host cell surface components and

•Specific viral surface glycoproteins of enveloped viruses, or

•Specific viral surface proteins of naked viruses.

350 MEDICAL

Chapter 4 • Medically ImportantViruses

These interactions (and the distribution of the receptors) determine viral

1.Host range (e.g., horses or humans)

2.Tissue specificity (e.g., liverversus heart; tropism)

Table ll-1.-1. SpecificViral Receptors to Know

Table ll-1.-2. Difference Between Naked and Enveloped Viruses

Viral Entry Into Host Cell

Viral entry is by

• Receptor-mediated endocytosis

•Uptake via coated pits

•Or for those enveloped viruses with fusion proteins via fusion of the cell membrane with the viral envelope

Macromolecular Synthesis

How do the various viruses make their mRNA? mRNA production is diagrammed below.

•The major types of viral genomes are shown on the right.

•The replication intermediates necessary to make mRNA are shown in the gray area.

MEDICAL 351

Chapter It • Medically ImportantViruses

Release ofViruses

Naked viruses lyse the host cells. Thus, there are no persistent productive infections . with naked viruses (only cytolytic productive or latent infections).

Release of enveloped viruses: Budding leads to cell senescence (aging), but cells may produce a low level of virus for years as occurs in chronic hepatitis B.

Nucleocapsid

Figure 11-4-8. Release of Enveloped Virus

The glycoproteins on the enveloped viral surface are essential for viral infectivity.

MEDICAL 353

Section II • Microbiology

HOST RESISTANCE TO VIRAL INFECTION

Primary Defenses

•Skin barrier (dead keratinized cells impervious to viruses)

•Skin has acids and other inhibitors produced by normal bacterial flora

•Mucociliary elevator

Immune Defense

Innate immune response

•Interferon

•Complement

•Natural killer cells

Adaptive immune response

•Antibody

•Cytotoxic T lymphocytes

Interferon Production

Interferons (IFNs) are a family of eukaryotic cell proteins classified according to the cell of origin. IFN-alpha and IFN-beta are produced by a variety of virus-infected cells. They:

•Act on target cells to inhibit viral replication.

•Do not act directly on the virus.

•Are not virus-specific.

•Are species-specific (e.g., mouse IFN versus human IFN).

Interferon inhibits viral protein synthesis

•Through activation of an RNA endonuclease, which digests viral RNA.

•By activation (by phosphorylation) of protein kinase that inactivates eIF2, inhibiting viral protein synthesis.

Exogenous human IFN (produced by recombinant DNA technology) maybe used in antiviral therapy for chronic, active HBV and HCV infections.

356 MEDICAL

Chapter 4 • Medically ImportantViruses

Table ll-1.-6. Hepatitis B Terminology and Markers

Table ll-1.-7. Hepatitis B Serology

MEDICAL 359

Chapter If • Medically ImportantViruses

DNAVIRUSES: CHARACTERISTICS

AllDNA viruses:

•Are double-stranded, except parvovirus

•Are icosahedral, except poxviruses, which are a brick-shaped "complex"

•Replicate their DNA in the nucleus, except poxvirus

Table ll-lf-8. DNA Viruses*

* Mnemonic: £ardon £apaf!,sHeHas £ox

** Poxviruses have a virion-associated transcriptase (DNA dependent RNA polymerase), so it can transcribe its own DNA in the cytoplasm and make all ofthe enzymes and factors necessary for replication ofthe poxvirus DNA in the cytoplasm.

***Hepadnaviruses: DNAviruses that carry a DNA polymerase with reverse transcriptase activity to synthesize an RNA interme­ diate that is then used to make the genomic DNA. Hepatitis B is partially double-stranded with one complete strand.

MEDICAL 361

Chapter 4 • Medically ImportantViruses

MEDICAL 363

Section II • Microbiology

364 MEDICAL

Chapter 4 • Medically ImportantViruses

Diagnosis

•Cutaneous--dinical grounds

•Genital--finding of koilocytic cells (cells with perinuclear cytoplasmic vacuolization and nuclear enlargement) in Pap smears

•In situ DNA probes and PCR can be used to confirm any diagnosis and type the HPV strain involved

Treatment

•Cryotherapy, electrocautery, or chemical means (salicylic acid)

•Imiquimod (induces proinflammatory cytokines), interferon-a, and virus­ specific cidofovir

Prevention

•A vaccine composed of HPV capsid proteins produced by recombinant DNA technology

•Safe sex practices

POLYOMAVIRIDAE

Table ll-1.-9. Summary ofPolyomaviridae

MEDICAL 365

Chapter 4 • Medically ImportantViruses

HEPADNAVIRIDAE (see previous discussion)

HERPESVIRIDAE

Virus Characteristics

•Large dsDNA

•Enveloped, icosahedral

•Derives envelope from nuclear membrane

•Intranudear inclusion bodies

•Establishes latency

Figure 11-4-1 6. Herpesvirus

Viruses ofMedical Importance

•Herpes simplex virus 1 and 2 (HSV)

•Varicella-zoster virus (VZV)

•Epstein-Barr virus (EBV)

•Cytomegalovirus (CMV)

•Human herpesvirus 6 (HHV-6)

•Human herpesvirus 8 (HHV-8)

Section II • Microbiology

• Meningoencephalitis

Fever, headache, and confusion

Focal temporal lesions and perivascular cuffing If untreated, 70% mortality rate

HSV- 1: high fatality HSV-2 (usually mild)

• Genital infections

Painful genital vesicles

Systemic effects can include fever, malaise, and myalgia

Latency in the sacral nerve ganglia

• Neonatal herpes

Infection during passage through infected birth canal Infections are usually severe:

0Disseminated with liver involvement and high mortality

0Encephalitis, high mortality

oSkin, eyes, or mouth

Diagnosis

•Oral lesions--clinical

•Encephalitis

PCR on CSF

Large numbers of RBCs in CSF

•Genital infections--Tzank smear to show the formation of multinucle- ated giant cells and Cowdry type A intranuclear inclusions has been largely replaced by immunofluorescent staining, which can distinguish HSV- 1 from HSV-2

Treatment-Acyclovir is a nucleoside analog that is only activated in cells infected with HSV-1, HSV-2 or VZV. This is because the virus thymidine kinase is required to activate the drug by placing the first phosphate on the drug, followed by the phos­ phorylation via cellular enzymes. Resistance to acyclovir occurs due to a mutation in the thymidine kinase. Famciclovir, valacyclovir, and penciclovir are alternatives if resistance develops.

368 MEDICAL

Chapter It • Medically ImportantViruses

MEDICAL 369

370 MEDICAL

372 MEDICAL

374 MEDICAL

Chapter It • Medically ImportantViruses

Diagnosis

•Clinical

•Guarnieri bodies found in infected cells (intracytoplasmic)

Treatment-supportive care

Prevention--ve,:liattenuatedvaccine

MEDICAL 375

378 MEDICAL

Chapter 4 • Medically ImportantViruses

PICORNAVIRIDAE

Figure 11-4-20. Picornavirus

Family Characteristics

•Small, naked, icosahedral

•Positive-sense ssRNA

•Summer/fall peak incidence

•Resistant to alcohol, detergents (naked capsid)

•Divided into genera: Enteroviruses:

Fecal-oral transmission, do not cause diarrhea Peak age group <9 years

Stable at pH 3 Rhinoviruses:

Not stable under acidic conditions Growth at 33°C

Heparnavirus

Viruses ofMedical Importance

•Enteroviruses (acid stable) Polio virus

Coxsackie virus A Coxsackie virus B Echoviruses

•Rhinoviruses (acid labile)

•Heparnaviruses--HAV

MEDICAL 379

Chapter If • Medically ImportantViruses

FLAVIVIRIDAE

Family Characteristics

•Enveloped, icosahedral

•Positive-sense ssRNA

•Arthropod-borne (arboviruses)

Viruses ofMedicalImportance

•St. Louis encephalitis virus (SLE)

•West Nile encephalitis virus (WNV)

•Dengue virus

•Yellow fever virus (YFV)

•Hepatitis C virus (HCV; discussedwith the hepatitis viruses)

Definition ofabbreviations: FUO, fever of unknown origin; SLE, St. Louis encephalitis virus; WNV, West Nile encephalitis virus; YFV, yellow fever virus.

MEDICAL 381

Section II • Microbiology

TOGAVIRIDAE

Family Characteristics

•Enveloped, icosahedral

•Positive-sense ssRNA

Figure 11-4-21 . Togavirus

Viruses ofMedical Importance

• Alphaviruses (arboviruses)

Eastern equine encephalitis virus (EEE)

Western equine encephalitis virus (WEE)

Venezuelan equine encephalitis virus (VEE)

•Rubivirus

- Rubella

Table ll-1.-14. SummaryofTogaviridae

Definition ofabbreviations: CRS, congenital rubella syndrome; EEE, Eastern equine encephalitis virus; VEE, Venezuelan equine encephalitis virus; WEE, Western equine encephalitis virus.

*Congenital rubella syndrome-patent ductus arteriosis, pulmonary stenosis, cataracts, microcephaly, deafness. The effects are more serious ifthe maternal infection is acquired during the first 16 weeks' gestation.

382 MEDICAL

Section II • Microbiology

Conditions ofEarly Symptomatic Period

•Bacillary angiomatosis (disseminated bartonellosis)

•Candidiasis (oral or persistent vulvovaginal)

•Cervicaldysplasia or carcinoma in situ

• Constitutional symptoms (fever 38.5°C or diarrhea lasting >1 month)

•Hairyleukoplakia

•Idiopathic thrombocytopenic purpura

•Listeriosis

•Pelvic inflammatory disease (especiallywith abscess)

•Peripheral neuropathy

Conditions Associated with AIDS

•Encephalopathy, HIV-related

•Pneumonia, recurrent (leading cause ofdeath)

•Fungal infections

•Candidiasis ofesophagus, bronchi, trachea, or lungs

•Coccidioidomycosis, disseminated or extrapulmonary

•Cryptococcosis, extrapulmonary

•Histoplasmosis, disseminated or extrapulmonary

•Pneumocystis jirovecii pneumonia

•Malignancies

Invasive cervical carcinoma

Kaposi sarcoma; Burkitt, irnmunoblastic, or primary CNS lymphoma

388 MEDICAL

Section II • Microbiology

Prevention

•Education/safe sex

•Blood/organ screening

•Infection control

•Vaccine development (currently none available)

390 M EDICAL

Section II • Microbiology

Diagnosis---erologys

Treatment

•Supportive

•Ribavirin (experimental)

Prevention--live, attenuated vaccine, MMR

Mumps Virus

Distinguishing Characteristics

•Negative-sense ssRNA

•Helical

•Enveloped

•Single HN glycoprotein, also F protein

•Single serotype

Reservoir-human respiratory tract

Transmission-person to person via respiratory droplets

Pathogenesis--lytic infection ofepithelial cells ofupper respiratorytract and parotid glands spread throughout body.

Diseas mumps

•Asymptomatic to bilateral parotitis with fever, headache, and malaise

•Complications include pancreatitis, orchitis (leads to sterility in males), and meningoencephalitis

Diagnosis

•Clinical

•Serology; ELISA, IFA, hemagglutination inhibition

Treatment--supportive

Prevention--live,attenuated vaccine, MMR

394 MEDICAL

Section II • Microbiology

396 MEDICAL

Chapter 4 • Medically ImportantViruses

Diagnosis

•Clinical

•Negri bodies, intracytoplasmic inclusion bodies (brain biopsy)

•DFA (impression smears of corneal epithelial cells), PCR (usually too late)

Treatment

•If symptoms are evident: none

•If suspect:

Poste:>qJosure prophylaxis

One dose of human rabies immunoglobulin (hRIG)

-Five doses of rabies vaccine (day of, 3, 7, 14, 28)

-Killed virus vaccine

Prevention

•Vaccine for high-risk individuals

•Vaccination program for domestic animals (U.S.)

MEDICAL 397

Section II • Microbiology

FILOVIRIDAE

Family Characteristics

•Negative-sense ssRNA

•Enveloped, helical

•Filamentous

Viruses of Medical Importance

•Ebola virus

•Marburg virus

398 MEDICAL

Chapter 4 • Medically ImportantViruses

MEDICAL 399

Section II • Microbiology

• Antigenic shift

Influenza A only

Rare genetic reassortment

Coinfection of cells with two different strains of influenza A (HSNl and H3N2); reassortment of segments of genome

Production of a new agent to which population has no immunity Responsible for pandemics

Disease--influenza

•Headache and malaise

•Fever, chills, myalgias, anorexia

•Bronchiolitis, croup, otitis media, vomiting (younger children)

•Pneumonia/secondary bacterial infections

•Can lead to Reye syndrome or Guillain-Barre syndrome

Diagnosis

•Rapid tests (serology)

•Clinical symptoms plus season

Treatment

•Amantadine/rimantadine (current isolates are commonly resistant)

-Inhibit viral uncoating

-Administer orally

•Zanamivir/oseltamivir

Neuraminidase inhibitors

Zanamivir is inhaled

Oseltamivir is given orally

Prevention

•Killed vaccine

-Two strains of influenza A (H3N2, HlNl, for example) and one strain of influenza B are incorporated into the vaccine

•Live, attenuated vaccine

Intranasal administration

Similar composition

Currently recommended for children >5 years

400 MEDICAL

Chapter4 • Medically ImportantViruses

• Mostly arboviruses, except Hantavirus

Viruses of Medical Importance

•California encephalitis

•Lacrosse encephalitis

•Hantavirus (sin nombre)

Table ll-1.-22. Summary of Bunyaviridae

PL MEDICAL 401

Chapter It • Medically ImportantViruses

DOUBLE-STRANDED RNAVIRUSES

REOVIRIDAE

Figure 11-4-30. Reovirus

Definition ofAbbreviations: CTFV; Colorado tick fever virus, ELISA; enzyme-linked immunosorbent assay.

M EDICAL 403

Chapter 4 • Medically ImportantViruses

•Infection with a virus carrying a v-onc: e.g., infection with a retrovirus carrying viral oncogenes such as src. The gene was probably picked up by a provirus inserted near a cellular oncogene picking up copies of c-onc. Viral progeny then contain the new oncogene now called v-onc. v\lhen a new cell is infected with the recombinant virus, the oncogene is now under the tran­ scriptional control of the viral enhancer/promoter.

•Interaction between the products of oncogenes and tumor suppressor genes. Proteins E6 and E7 of the human papilloma virus combine with and inacti­ vate the p53 and Rb, respectively.

Specific Viruses Associated with Human Cancers

EBV

•Burkitt lymphoma (BL), nasopharyngeal, and thymic carcinoma

•BL occurs only in malarial regions; the plasmodia are thought to produce a slight immunosuppression.

•EBV stimulates B-cell replication and eventually, if a translocation of c-myc to the DNA region where genetic rearrangements involved in antibody synthesis occurs, BL develops.

Chronic HBV

Primary hepatocellular carcinoma

Chronic HCV

Primary hepatocellular carcinoma

HPV

•Cervical carcinoma

•Mechanism: inactivation of tumor suppressor gene

HTLV-1

•CD4+ T-cell leukemia/lymphomas

•Provirus insertion or capture

HTLV-2

• Hairy cell leukemia

MEDICAL 405

Section II • Microbiology

PRION DISEASES

Table ll-4-27. Slow ConventionalViruses (Viruses)

406 MEDICAL

Chapter If • Medically ImportantViruses

VIRAL GENETICS

Phenotypic Mixing

Figure 11-4-31. Phenotypic Mixing

•Related viruses coinfect cell (virus A and virus B).

•Resulting proteins on the surface are a mixture capsid ofAB around nucleic acid of either A or B.

Phenotypic Masking

Figure 11-4-32. Phenotypic Masking

•Related viruses coinfect cell (virus A and virus B).

•Capsid of proteins of virus A form around nucleic acid of B.

Complementation

•Two related defective viruses infect the same cell. If they are defective in dif­ ferent genes, viral progeny (still with defective DNA) will be formed.

Figure 11-4-33. Complementation: Mutations in Different Genes

M EDICAL 407

Section II • Microbiology

If they are defective in the same gene, no progeny willbe formed.

no C gene product :. no virus made

Figure 11-4-34. Complementation: Mutations in Same Genes

•Coinfection of hepatitis B and D is a clinical example of complementation where HBV supplies the needed surface antigen for hepatitis D.

Genetic Reassortment = Genetic Shift

•Two different strains of a segmented RNA virus infect the same cell.

•Major new genetic combinations are produced through "shuffling;'result­ ing in stable and dramatic changes.

In same cell

Figure 11-4-35. Genetic Reassortment in Influenza A

Genetic Drift

•Minor antigenic changes from mutation

•Occurs in many viruses, particularly RNA ones

•Most noted in HIV and influenza

Viral Vectors

•Recombinant viruses are produced that have combinations of human replacement genes with the defective viral nucleic acid.

408 MEDICAL

Chapter If • Medically ImportantViruses

Review Questions

1. A 5-year-old presents to the pediatrician with complaints of a sore throat. Her mother also noticed that both ofher eyes were slightly red. Examination reveals rhinopharyngitis with bilateral conjunctivitis. What activity likely led to the above illness?

(A)Hiking in a heavily wooded area

(B)Eating undercooked shellfish

(C)Playing with toys in a day care center

(D)Traveling to a developing country

(E)Swimming in a community pool

2. Serologic test results from a hepatitis patient reveal: anti-HBc positive, HBsAg positive, and anti-HBs negative. The correct interpretation of the patient's status is

(A)No longer contagious

(B)Immune to hepatitis B virus

(C) Evidence of receiving hepatitis B vaccination

(D)Hepatitis B virus chronic carrier state

(E)Impossible to have both surface antigen and core antibody positive

3.A 6-year-old girl presents to the emergency department with a fever and a lacy body rash. Her mother says that yesterday the rash was only on her face, but by this morning, had spread to her trunk and extremities. Which of the following agents is most likely?

(A)Bl9

(B)HHV-6

(C)Measles

(D)Rubella

(E)Varicella zoster virus

4.The best prospects for treatment and cure of microbial diseases are always those unique factors of a pathogen's life cycle that can be altered without affecting the survival of the host's own cells. In HIV, one such therapeutic target would be the products of the pol gene, which codes for the reverse transcriptase unique to the retroviral life cycle. If it were possible to ablate expression of the HIV pol gene, what other aspect of the virus's life cycle would be directly altered?

(A)Transcription from proviral DNA

(B)Production of viral mRNA

( C) Integration of proviral DNA

(D)Nucleocapsid

(E)Viral maturation

MEDICAL 409

Section II • Microbiology

5. A 28-year-old male ERresident was accidentally stuck with a needle from a hepa­ titis B virus-positive patient. He was too embarrassed to tell his attending of his mistake. Two months later, he began to feel fatigued and lost his appetite. When he ordered a hepatitis B serologic panel, he received the results as follows:

HBsAg +

HBsAb

HBcAb +

HBeAg +

HBeAb

What is the status of the resident?

(A) Acute infection (B) Chronic infection

(C) Fulminant infection

(D)Immune

(E)Uninfected

6.A prison inmate who was diagnosed with hepatitis 6 months ago is tested for his progress with the folllowing results:

HBsAg

HBsAb +

HBcAb +

HBeAg

HBeAb +

What is the status of the patient?

(A) Acute infection (B) Chronic infection

(C) Fulminant infection

(D)Immune

(E)Uninfected

7.A 10-year-old boy is brought to the emergency department with a high fever, chills, headache, and nausea. He vomits at admission, where his temperature is 104.2°F, and he begins to hallucinate. A CT scan reveals encephalitis in one temporal lobe. Which of the following causal agents is most likely?

(D)St. Louis encephalitis

(E)West Nile virus

410 MEDICAL

Chapter It • Medically ImportantViruses

8.A 60-year-old woman who recently received a liver transplant develops a high fever and severe dyspnea with a dryhacking cough. Chest x-ray reveals bilateral interstitial infiltrates that are diffuse.Which ofthe following agents is most likely responsible for her condition?

(A)Adenovirus

(B)Cytomegalovirus

(C) Influenza virus

(D)Respiratorysyncytialvirus

(E) Rhinovirus

9.An 8-year-oldboyfromIndiawasbrought to the emergency department while visiting the U.S. because of a flaccid paralysis in his lower extremities. His mother explains that the child had a flu-like illness a couple of weeks earlier. How was the agent in the above case likely acquired?

(A)Fecal-oral

(D)Sexual

(E)Tick

10.A 5-year-old girl presents with a fever and a generalized macular rash that is most dense on the scalp andtrunk ofthe body. Several waves oflesions appear, one after another, and evolve rapidlyinto vesicles andthen pustules over several days. The most likely disease and causal agent is

(A)Exanthem subitum due to cytomegalovirus

(B)Chickenpox due to the varicella-zoster virus

(C) Whitlow infection due to herpes simplex virus type 1

(D)Herpetic gingivostomatitis due to the varicella-zoster virus

(E)Infectious mononucleosis due to the Epstein-Barr virus

1 1. Infection ofappropriatecellswith a compositevirus made up ofCoxsackievirus capsid components and poliovirus RNA would yield progenywhich would

(A)Have the host cell range of Coxsackie virus

(B)Also be composite viruses

(C) Show phenotypic mixing

(D)Have a recombinant genome consisting ofboth Coxsackie and poliovirus

(E)React with Sabin-vaccine-induced antibodies

12.An epidemic of nausea, vomiting, and watery diarrhea breaks out on ship­ board during a cruise to theVirgin Islands. Which ofthe following accurately describes the most likely causal agent?

(A)Acid-fast oocysts

(B)Enveloped DNA virus

(C) Enveloped RNA virus

(D)Nonenveloped DNA virus

(E)Nonenveloped RNAvirus

MEDI CAL 411

Section II • Microbiology

13.To design a vaccine against HIV infection, a logical goal would be to alter some native molecule or product of the virion in order to make it highly immuno­ genic. Ifyou wished to prevent the attachment ofthe virus to helper T lympho­ cytes, which molecule or family of molecules might best be targeted?

(A)gp41

(B)gpl20

(C)nucleocapsid protein

(D)p l 7

14.A woman in her late twenties presents to the emergency department disorient­ ed and confused. She is unable to remember where she lived or even her phone number. She is admitted for observation and testing and begins to hallucinate and salivate excessively. On the east coast of the United States, what is the most common reservoir of this disease?

(A)Bat

(B)Cat

(C)Dog

(D)Fox

(E)Raccoon

15. An 1 1-month-old infant was brought to the emergency department with difficulty breathing and wheezing. History and physical examination reveal a slight fever, cough, and rhinorrhea that began about 2 days before. Analysis of the sputum reveals normal flora with the presence of giant multinucleated cells. Which of the following is the most likely cause?

(A)Bl9

(B)Influenza

(C)Parainfluenza

(D)Measles

(E)Respiratory syncytial virus

16.A 37-year-old executive for a local Health Maintenance Organization comes to your office because he has developed multiple blister-like lesions on his penis over the last 1-2 days. They are somewhat painful, and he is worried that he has AIDS. He denies homosexuality and intravenous drug abuse and had an HIV test prior to his marriage 3 years ago. He reports several similar episodes several years ago when he worked as a photographer in Nepal. He was never told what they were, and they resolved over several days without any treatment. His physical examination is remarkable only for the presence of 6-8 vesicular lesions 3-4 mm in diameter on the glans of the penis. There is no crusting, drainage, or bleeding. The lesions are moderately tender and there is mild inguinal adenopathy bilater­ ally. How does the causal agent produce its messenger RNA?

(A)By producing a positive sense intermediate

(B)By direct translation from the genome

(C)By transcription from proviral DNA

(D)By producing a negative sense intermediate

(E)By transcribing from the genomic DNA

(F)By reverse transcription from the genome

(G) By semi-conservative replication

412 M EDICAL

Chapter If • Medically ImportantViruses

17. Several individuals in the central United States from the ages of 5 to 25 have come down with symptoms of nausea, vomiting, and swelling of the parotid glands. Which of the following can be a complication of the above disease?

(A)Guillain-Barre Syndrome

(B)Glomerulonephritis

(C) Orchitis

(D) Multiple sclerosis

(E) Reye syndrome

18. In the U.S., a baby has the greatest chance of acquiring which virus in utero?

(A)Cytomegalovirus

(B)Hepatitis B virus

(C)Herpes simplex virus

(D)Respiratory syncytial virus

(E)Rubella virus

19.Which ofthese viruses has RNA forboth its genome and replicative intermediate?

(A)Cytomegalovirus

(B)Hepadnavirus

(C)Retroviruses

(D)Togaviruses

(E)Poxvirus

20.What is the most common lab testing method for diagnosing infectious mono­ nucleosis?

(A)The Monospot test to detect EBV-specific antibody

(B)An assay for Epstein-Barr nuclear antigen

(C) The presence of atypical lymphocytes in the blood establishes the etiology

(D)A test for heterophile antibody, which cross-reacts with antigens found on a variety of animal red blood cells

(E)A simple procedure is done to isolate EBV from saliva, blood, or lymphoid tissue

21.What virus is noted for genetic reassortment, which leads to major pandemics about once every 10 to 1 1 years?

(A)Adenovirus

(B)Herpes virus

(C) Human immunodeficiency virus (HIV)

(D)Influenza virus

(E)Poliovirus

MEDICAL 413

Section II • Microbiology

22.What virus is noted for such a high incidence of genetic drift that more than one antigenic variant can be isolated from most infected individuals who have high viral titers?

(A)Adenovirus

(B)Herpes virus

(C) Human immunodeficiency virus (HIV)

(D)Influenza virus

(E)Poliovirus

23.A 19-year-old male college student reports sore throat and extreme fatigue fol­ lowing even normal non-taxing tasks like getting dressed and going down to breakfast. He tells you that he has been sick for several weeks, that he has been feverish, and that his girlfriend now appears to be getting the same thing. His tonsils are inflamed with a white exudate adhering; cervical lymphadenopathy is prominent, as is splenomegaly. The most likely causal agent is

(A)ssDNA, naked icosahedral virus

(B)dsDNA, naked icosahedral virus

(C)dsDNA, enveloped complex virus

(D)dsDNA, enveloped icosahedral virus

(E)dsRNA, naked segmented virus

(F)-ssRNA, segmented, enveloped and helical virus

(G)-ssRNA, bullet-shaped, helical virus

(H)-ssRNA, naked, helical virus

(I)+ssRNA, naked, icosahedral virus

CJ) +ssRNA, enveloped, icosahedral virus

(K)+ssRNA, enveloped, diploid virus

24.Cataracts and patent ductus arteriosus in a newborn suggest in utero infection with what viral family?

(A)Adenovirus

(B)Paramyxovirus

(C)Parvovirus

(D)Picornavirus

(E)Reovirus

(F)Togavirus

25.What is the primary means of spread for measles?

(A)Animal bite

(B)Fecal-oral

(C)Fomite spread

(D) Respiratory droplet spread

(E)Sexual contact

(F)Transfusion or intravenous drug abuse

(G) Tick bite

414 MEDICAL

MEDICAL 415

Section II • Microbiology

2.Answer: D. The presence ofhepatitis B surface antigen and the absence ofthe surface antibody (anti-HBs) indicate either an acute HBV infection (ifpatient has had the disease for only a short time) or a chronic carrier state (ifthe hepa­ titishas beengoingon foratleast 6 months). Because acute HBV is not a choice, choice D then becomes the correct answer. Choice B would be a right answer ifHBsAg had been negative and HBsAb positive. Core antibodies would not be present ifthe person is onlyvaccinated (choice C). Also, HBsAg should notbe present in a detectable amount fromvaccination. HBeAg and HBeAb are cor­ related to how contagious the patient might be, and these serologic results were not given (choice A).

3.Answer: A. The clues are lacy body rash preceded by a facial rash in a school aged child with fever. HHV-6 (choice B) is the causal agent of roseola, which is fever, followed by a lacy body rash in infants. Measles (choice C) is identi­ fied bycough, coryza, andconjunctivitiswith photophobia, Koplik spots, and an exanthematous rash beginning below the ears then spreading to the trunk and extremities. Rubella (choice D) is the causal agent of German measles, which involves a rash beginning at the forehead and spreading down.

4.Answer: C. The pol gene codes for reverse transcriptase, integrase, and prote­ ase. Reverse transcriptase creates the provirus and integrase allows the proviral DNA to be integrated, apparently at a random site, into a chromosome in the host cell. Ofthe distractors, both choices A and B are accomplished using the

host cell's RNA polymerase. Choice D is a function ofthegag gene, and choice E is controlled by tat and rev genes.

5.Answer: A. The presence of HBsAg, HBcAb, and HBeAg are all indicators of an acute infection at 2 months postexposure. It is too earlyto identify a chronic infection (choice B), but the presence of HBsAg after 6 months is the main indication of a chronic infection. With a fulminant infection (choice C), the

patient's symptoms are usually much more serious, likely a superinfection with hepatitis D or the delta agent. Ifhe were immune (choice D), he wouldhavehad HBsAb in his serum. Since he has hepatitis B viralantigensin his blood, choice

E is wrong.

6.Answer: D. The inmate is immune, as he has a complete complement of anti­ viral antibodies.

7.Answer: B. This patient has herpes simplex encephalitis, whch typically affects the temporal lobes. California encephalitis (choice A) affects older children in the middle and northwestern U.S. The polio virus (choice C) causes a flaccid paralysiswith no sensoryloss, and does not occur in theUnitedStates. St. Louis encephalitis (choice D) and the West Nile virus (choice E) usually affect older individuals.

8.Answer: B. The clues are transplant patient with interstitial pneumonia; CMVis the most common cause. Adenovirus (choice A) is associated with conjunctivitis and acute respiratorydisease in militaryrecruits, amongother diseases. Although influenza (choice C) can cause pneumonia, there is no mention of season, and

CMV is still the most common cause in transplant patients. Respiratorysyncytial virus (choice D) is usually seen in children (especially premature infants), and rhinovirus (choice E) causes the common cold.

9.Answer: A. Polio is caused bythe poliovirus. The clues are flaccid paralysis and India, and polio is transmitted bythe fecal-oral route.

10.Answer: B. The clinical presentation is consistent with chickenpox caused

by VZV Exanthem subitum is caused by human herpes virus 6, not by CMV Herpetic gingivostomatitis refers to herpes simplex type l, not VZV. Infectious

416 MEDICAL

Chapter It • Medically ImportantViruses

mononucleosis is a lymphadenopathy and herpetic whitlow is a painfulherpes infection ofthe nail bed.

1 1. Answer: E. The only nucleic acid in the composite parental virus is the RNA belonging to poliovirus. Thus, only poliovirus is made. The only role the Cox­ sackie virus would play in the infection is to bind to the host cell and stimulate the uptake of the composite virus. Once uncoating takes place, the Coxsackie components play no further role. A perfect poliovirus willhave been made. The progeny willhave the host-cell range ofpolio (choice A) because that is what they'll be. There is no genetic material coding for the Coxsackie components,

so you cannot get a composite (choice B). No capsid components ofCoxsackie willbe made; there can be no mixing (choice C). There was o_nly one type of

RNA; there can never be recombination (choice D). Sabin is a polio-specific vaccine, and poliovirus willbe produced.

12.Answer: E. A common cause ofgastroenteritis on cruise ships is the Norovirus. Norovirus is a member ofthe Caliciviridae family and is a nonenveloped RNA virus. Acid-fast oocysts (choice A) refer to persistent diarrhea caused by Cryp­ tosporidium parvum or Isospora belli, usually seen in AIDS patients. Enveloped DNA and RNAviruses (choicesB andC) cannotbe transmittedviathefecal-oral route orlive in the gastrointestinal tract because ofthe instabilityofthe envelope. A nonenveloped DNAvirus (choice D) wouldbe consistent with adenoviral gas­ troenteritis,which is notthe most likely cause ofcruise ship gastroenteritis.

13.Answer: B. Gpl20 is the surface antigen ofHIVthat mediates its attachment to CD4 lymphocytes. Gp41 is a transmembrane glycoprotein, and p24, pl7, and nucleocapsid protein are all internal molecules, which would rarely be acces­ sible to the immune response.

14.Answer: E. This patient has rabies, which exhibits these neurologic symptoms. In the eastern United States, the primary reservoir is raccoons.

15. Answer: E. An infant with difficulty breathing, wheezing, and giant multinu­ cleated cells (syncytia) is likelyto have respiratory syncytial virus. B19 (choice A) and influenza (choice B) would not show giant multinucleated cells, and B19 does not usually cause breathing difficulty. Parainfluenza (choice C) causes croup, which exhibits the swelling ofthe larynx and the seal-like bark­ ing cough. There is no mention ofrash or Koplik spots, which would indicate the measles (choice D).

16.Answer: E. The virus is HSV 2, a herpesvirus,which is a dsDNA virus that uses the mechanisms ofour own cellsto transcribe an RNA strand from its genomic DNA and use the transcribed RNA as a messenger RNA. Of the distractors: choice A is the technique used by the negative-sense RNAviruses; choice B is used by the positive-sense RNA viruses; choice C is used by the retroviruses; choice D is used duringthe genomic duplication ofpositive sense RNAviruses; choiceF would not produce RNA; and choice G is used in genomic replication by most DNA viruses.

17.Answer: C. The disease is mumps. The complication often seen in adult males is orchitis, which can lead to sterility.

18.Answer: A. CMVisanextremelycommonvirus and crosses the placenta often­ times without causing obvious symptoms. Fortunately, rubella, which is highly teratogenic particularly in early pregnancy, is generally prevented by routine

vaccination in childhood or at least 16 weeks prior to pregnancy. A small per­ centage ofhepatitis B infections may occur in utero. HSV 2 willonly cross the placenta ifthe mother acquires herpes for the first time during her pregnancy.

MEDICAL 417