Microbiology- Virology (HIV and Prions)

Question 1

HIV Characteristics

Answer 1

Diploid genome (2 molecules of RNA).

Reverse transcriptase synthesizes dsDNA from genomic RNA; dsDNA integrates into host genome.

Virus binds CD4 as well as a coreceptor, either CCR5 on macrophages (early infection) or CXCR4 on T cells (late infection).

Homozygous CCR5 mutation = immunity.
Heterozygous CCR5 mutation = slower course.

Question 2

HIV structural genes

Answer 2

The 3 structural genes (protein coded for):
Env (gp120 and gp41):
- Formed from cleavage of gp160 to form envelope glycoproteins.
- gp120—attachment to host CD4+ T cell.
- gp41—fusion and entry.

Gag (p24 and p17)—capsid and matrix
proteins, respectively.

Pol—reverse transcriptase, aspartate protease,
integrase.

Question 3

HIV diagnosis

Answer 3

Presumptive diagnosis made with HIV-1/2 Ag/Ab immunoassays. These immunoassays detect viral p24 Ag capsid protein and IgG Abs to HIV-1/2. Very high sensitivity/specificity.

⊕ tests are confirmed with HIV-1/2 Ab differentiation immunoassays which determine whether patient has HIV-1 or HIV-2.

If inconclusive differentiation assay, an HIV-1 nucleic acid amplification test (NAAT) is performed; if the NAAT is ⊝, patient had false positive initial Ag/Ab immunoassay.

Viral load tests determine the amount of viral RNA in the plasma. High viral load associated with poor prognosis. Also use viral load to monitor effect of drug therapy.

AIDS diagnosis ≤ 200 CD4+ cells/mm3 (normal: 500–1500 cells/mm3). HIV ⊕ with AIDS-defining condition (eg, Pneumocystis pneumonia) or CD4+ percentage < 14%.

Question 4

Four stages of untreated infection:

Answer 4

4 F´s

1. Flu-like (acute)
2. Feeling fine (latent)
3. Falling count
4. Final crisis

Question 5

Time course of untreated HIV infection

Answer 5

Pag 176

Question 6

Common diseases of HIV-positive adults 
CD4+ cell count < 500/mm3 
- Phatogen
- Presentation
- Findings

Answer 6

Candida albicans (Oral thrush. Scrapable white plaque, pseudohyphae on microscopy)

EBV (Oral hairy leukoplakia. Unscrapable white plaque on lateral tongue)

HHV-8 (Kaposi sarcoma. Biopsy with lymphocytic inflammation)

HPV (Squamous cell carcinoma, commonly of anus
(men who have sex with men) or cervix (women)

Question 7

Common diseases of HIV-positive adults 
CD4+ cell count < 200/mm3
- Phatogen
- Presentation
- Findings

Answer 7

Histoplasma capsulatum: Fever, weight loss, fatigue, cough, dyspnea, nausea, vomiting, diarrhea. Oval yeast cells within macrophages.

HIV: Dementia

JC virus (reactivation): Progressive multifocal leukoencephalopathy. Nonenhancing areas of demyelination on MRI.

Pneumocystis jirovecii: Pneumocystis pneumonia “Ground-glass” opacities on CXR

Question 8

Common diseases of HIV-positive adults 
CD4+ cell count < 100/mm3
- Phatogen
- Presentation
- Findings

Answer 8

Aspergillus fumigatus: Hemoptysis, pleuritic pain. Cavitation or infiltrates on chest imaging.

Bartonella henselae: Bacillary angiomatosis. Biopsy with neutrophilic inflammation.

Candida albicans: Esophagitis. White plaques on endoscopy; yeast and pseudohyphae on biopsy.

CMV: Retinitis, esophagitis, colitis, pneumonitis, encephalitis. Linear ulcers on endoscopy, cotton-wool spots on fundoscopy. Biopsy reveals cells with intranuclear (owl eye) inclusion bodies.

Question 9

Common diseases of HIV-positive adults 
CD4+ cell count < 100/mm3
- Phatogen
- Presentation
- Findings

Answer 9

Cryptococcus neoformans: Meningitis. Encapsulated yeast on India ink stain or capsular antigen ⊕

Cryptosporidium spp: Chronic, watery diarrhea. Acid-fast oocysts in stool

EBV: B-cell lymphoma (eg, non-Hodgkin lymphoma, CNS lymphoma). CNS lymphoma—ring enhancing, may be
solitary (vs Toxoplasma)

Mycobacterium avium–intracellulare, Mycobacterium avium complex: Nonspecific systemic symptoms (fever, night sweats, weight loss) or focal lymphadenitis.

Toxoplasma gondii: Brain abscesses. Multiple ring-enhancing lesions on MRI

Question 10

Prions

Answer 10

conversion of a normal (predominantly α-helical) protein termed prion protein (PrPc) to a β-pleated form (PrPsc), which is transmissible via CNS-related tissue (iatrogenic CJD) or food contaminated by BSE-infected animal products (variant CJD).

PrPsc resists protease degradation and facilitates the conversion of still more PrPc to PrPsc. Accumulation of PrPsc results in spongiform encephalopathy and dementia, ataxia, and death.

Question 11

Creutzfeldt-Jakob disease

Answer 11

rapidly progressive dementia, typically sporadic (some familial forms).

Question 12

Bovine spongiform encephalopathy

Answer 12

also known as “mad cow disease.”

Question 13

Kuru

Answer 13

acquired prion disease noted in tribal populations practicing human cannibalism.