USMLE Microbiology Syllabus

Which Mycobacterium causes disseminated disease in advanced AIDS, and at what CD4 count is prophylaxis indicated?

Mycobacterium avium-intracellulare (MAC) causes disseminated infection when CD4 counts fall below 50 cells/microliter; azithromycin prophylaxis is given. Treatment uses a macrolide plus ethambutol +/- rifabutin.

State the general rule distinguishing DNA viruses from RNA viruses regarding replication site and genome.

Most DNA viruses replicate in the nucleus (exception: poxviruses, in cytoplasm) and are double-stranded (exception: parvovirus, ssDNA). Most RNA viruses replicate in the cytoplasm (exceptions: influenza and retroviruses use the nucleus) and are single-stranded (exception: reovirus, dsRNA).

List the seven families of DNA viruses (mnemonic 'HHAPPPPy').

Hepadnavirus, Herpesvirus, Adenovirus, Poxvirus, Parvovirus, Papillomavirus, and Polyomavirus. All are double-stranded except Parvovirus (ssDNA), and all are enveloped except Papilloma, Polyoma, Adeno, and Parvo (naked).

Which DNA virus is the only single-stranded one, and what diseases does it cause?

Parvovirus B19 (ssDNA, naked). It causes erythema infectiosum (fifth disease, 'slapped-cheek' rash) in children, aplastic crisis in sickle cell disease, and hydrops fetalis if it infects a fetus by targeting erythroid precursors.

Contrast HSV-1, HSV-2, and VZV latency sites among the herpesviruses.

HSV-1 (oral/keratitis/temporal-lobe encephalitis) latent in the trigeminal ganglion; HSV-2 (genital/neonatal) latent in the sacral ganglia; VZV (chickenpox, then shingles) latent in dorsal root and trigeminal ganglia. All are enveloped dsDNA viruses with Cowdry A intranuclear inclusions.

What are the disease associations and cell tropism of EBV and CMV?

EBV (HHV-4) infects B cells via CD21, causing infectious mononucleosis (atypical Downey T cells, heterophile/monospot positive), Burkitt and Hodgkin lymphoma, nasopharyngeal carcinoma. CMV (HHV-5) causes mononucleosis (monospot-negative), congenital infection, and 'owl-eye' inclusions/retinitis in AIDS.

Which DNA virus subtypes cause cervical cancer, and what is the oncogenic mechanism?

Human papillomavirus (HPV) types 16 and 18. E6 protein degrades p53 and E7 inhibits Rb, disabling tumor suppressors and driving cervical, anal, and oropharyngeal carcinoma. Types 6 and 11 cause benign genital warts (condylomata).

How does hepatitis B virus (a hepadnavirus) differ from typical DNA viruses in replication?

HBV is a partially double-stranded DNA virus that uniquely uses a reverse transcriptase to replicate its genome through an RNA intermediate. HBsAg indicates infection, anti-HBs indicates immunity, and HBeAg indicates high infectivity.

List the major naked (non-enveloped) RNA viruses and one clinical association.

Naked RNA viruses (mnemonic: naked CPR and Hippo) — Calicivirus (Norovirus, gastroenteritis), Picornavirus (poliovirus, coxsackie, rhinovirus, HAV), Reovirus (Rotavirus, childhood diarrhea), and Hepevirus (HEV). Being naked, they are relatively resistant and often transmitted fecal-orally.

Why is influenza virus prone to pandemics, and what are the two mechanisms of change?

Influenza is a segmented, negative-sense ssRNA orthomyxovirus. Antigenic drift = minor point mutations in hemagglutinin/neuraminidase (yearly epidemics); antigenic shift = reassortment of genome segments between strains (major pandemics). Hemagglutinin binds sialic acid; neuraminidase releases virions (oseltamivir target).

What distinguishes positive-sense from negative-sense RNA viruses functionally?

Positive-sense (+) RNA can be directly translated by host ribosomes (its genome acts as mRNA, so purified genome is infectious). Negative-sense (-) RNA must first be transcribed to (+) mRNA by a virion-packaged RNA-dependent RNA polymerase (must bring its own polymerase).

Name the negative-sense RNA virus families (mnemonic 'Always Bring Polymerase Or Fail Replication').

Arenaviruses, Bunyaviruses, Paramyxoviruses, Orthomyxoviruses, Filoviruses, and Rhabdoviruses. All carry their own RNA-dependent RNA polymerase because their genome cannot be directly translated.

What are the key paramyxoviruses and their signature findings?

Measles (Koplik spots, cephalocaudal rash, risk of SSPE), Mumps (parotitis, orchitis, aseptic meningitis), Parainfluenza (croup / laryngotracheitis, 'seal-bark' cough), and RSV (bronchiolitis/pneumonia in infants; prevented with palivizumab). RSV requires the fusion (F) protein for multinucleated giant cells.

Which arbovirus family and vector cause dengue and yellow fever, and what is their genome?

Flaviviruses — positive-sense ssRNA, enveloped — transmitted by Aedes mosquitoes. Dengue can cause hemorrhagic fever/shock via antibody-dependent enhancement on secondary infection; yellow fever causes jaundice and councilman bodies in the liver.

What virus causes rabies, what is its shape, and what is its hallmark histologic finding?

Rabies virus (Rhabdovirus): a bullet-shaped, negative-sense ssRNA virus. It travels retrograde up axons via dynein to the CNS, producing eosinophilic cytoplasmic Negri bodies (classically in hippocampal and Purkinje neurons).

How does hepatitis C virus contribute to chronic disease and why is a vaccine difficult?

HCV is an enveloped, positive-sense ssRNA flavivirus. Its lack of proofreading (3'-5' exonuclease) and rapid mutation of envelope glycoproteins (E1/E2) generate quasispecies, causing chronic infection in most patients and thwarting vaccine development. It predisposes to cirrhosis and hepatocellular carcinoma.

What defines a retrovirus, and what is the central enzymatic step in its life cycle?

Retroviruses are enveloped, positive-sense, diploid (two identical +ssRNA copies) viruses that use reverse transcriptase (RNA-dependent DNA polymerase) to convert their RNA genome into dsDNA, which integrase then inserts into the host genome as a provirus.

Name the three essential structural/enzymatic genes of HIV and what each encodes.

gag (encodes structural core proteins p24 and matrix p17), pol (encodes reverse transcriptase, integrase, and protease), and env (encodes gp160, cleaved to surface gp120 and transmembrane gp41).

Describe how HIV gp120 and gp41 mediate host cell entry.

gp120 binds the CD4 receptor plus a coreceptor (CCR5 on macrophages early, CXCR4 on T cells late); gp41 then mediates fusion of the viral envelope with the host membrane. Homozygous CCR5-delta32 mutation confers resistance to infection.

What CD4 count thresholds define AIDS and predict specific opportunistic infections?

AIDS is defined by CD4 below 200 cells/microliter (or an AIDS-defining illness). Below 200: Pneumocystis jirovecii pneumonia; below 100: Toxoplasma encephalitis, Cryptococcus; below 50: CMV retinitis and disseminated MAC.

Which retrovirus besides HIV is oncogenic, and what malignancy does it cause?

Human T-cell lymphotropic virus type 1 (HTLV-1) causes adult T-cell leukemia/lymphoma and tropical spastic paraparesis (HTLV-associated myelopathy). Its Tax protein activates host transcription (NF-kB) promoting T-cell proliferation.

What are the main classes of antiretroviral drugs targeting the retroviral life cycle?

NRTIs and NNRTIs (inhibit reverse transcriptase), integrase inhibitors ('-tegravir'), protease inhibitors ('-navir', prevent Gag-Pol cleavage), and entry/fusion inhibitors (maraviroc blocks CCR5; enfuvirtide blocks gp41). Standard therapy (HAART) combines multiple classes.

What dimorphic behavior defines Candida albicans, and what does germ-tube formation indicate?

Candida albicans is a yeast that forms budding yeasts and pseudohyphae at 20-25 degrees C but true germ tubes/hyphae at 37 degrees C (in body/serum). Germ-tube formation at 37 degrees C is a rapid identifying test. It causes thrush, esophagitis (AIDS), vulvovaginitis, and disseminated candidemia.

Which yeast causes meningitis in AIDS patients, and how is it identified?

Cryptococcus neoformans: a heavily encapsulated yeast identified by India ink (clear halo) or mucicarmine-stained polysaccharide capsule, and by latex agglutination for capsular antigen (most sensitive). It is acquired from pigeon droppings and causes 'soap-bubble' lesions in the brain.

What is the temperature-dependent dimorphism of the systemic mycoses, and name the four classic agents?

They are 'mold in the cold (25 degrees C), yeast in the heat (37 degrees C)'. Agents: Histoplasma (intracellular in macrophages, Ohio/Mississippi River valleys, bird/bat droppings), Blastomyces (broad-based buds), Coccidioides (spherules with endospores, Southwest US), and Paracoccidioides ('captain's-wheel' budding).

How does Pneumocystis jirovecii present and how is it treated/prevented?

P. jirovecii (a yeast-like fungus) causes diffuse interstitial pneumonia (PCP) in AIDS with CD4 below 200, showing 'ground-glass' opacities and disc-shaped cysts on methenamine silver stain of bronchoalveolar lavage. Treatment and prophylaxis: trimethoprim-sulfamethoxazole (TMP-SMX).

Which mold causes angioinvasive disease with 45-degree acute-angle septate hyphae, and what are its clinical forms?

Aspergillus fumigatus: septate hyphae branching at acute (~45 degree) angles. Forms include allergic bronchopulmonary aspergillosis (ABPA, in asthma/CF), aspergilloma ('fungus ball' in a preexisting cavity), and invasive aspergillosis (immunocompromised, produces aflatoxin linked to hepatocellular carcinoma).

What mold causes mucormycosis, what is its hyphal morphology, and which patients are at risk?

Mucor and Rhizopus species: broad, nonseptate hyphae branching at wide (~90 degree) angles. They cause rhino-orbital-cerebral mucormycosis, invading through the cribriform plate, especially in diabetic ketoacidosis and neutropenic/immunocompromised patients; black necrotic eschars are characteristic.

What are the superficial dermatophyte molds, and what does a KOH prep or Wood's lamp show?

Dermatophytes — Microsporum, Trichophyton, and Epidermophyton — cause tinea (ringworm) infections of skin, hair, and nails. KOH prep of skin scrapings shows branching septate hyphae; some Microsporum species fluoresce under a Wood's (UV) lamp. Treated with topical or oral azoles/terbinafine.

Contrast Sporothrix schenckii infection with typical mold infections.

Sporothrix schenckii is a dimorphic fungus ('cigar-shaped' yeast at 37 degrees C) acquired by thorn/rose or sphagnum-moss inoculation ('rose gardener's disease'). It causes local pustules/ulcers that ascend along lymphatics (nodular lymphangitis), treated with itraconazole (or potassium iodide for cutaneous disease).