HIV

Question 1

1. List and describe the basic structural components of the human immunodeficiency virus (HIV).

Answer 1

enveloped RNA retrovirus with genes for Pol (reverse transcriptase, protease and integrase), Env (forms gp120 and gp41 for attachment and fusion) and Gag (viral core)

Question 2

1. Describe the life cycle of human immunodeficiency virus (HIV).

Answer 2

i. Attachment of gp120 to CD4 receptor and chemokine co receptor; fusion of membrane and release into host cell
ii. Reverse transcriptase RNA-> DNA, integrase melds DNA copy to host genome
iii. Transcription of provirus and viral protease cleaves polyproteins
iv. Assembly of nucleocapsid, particle budding, acquiring of envelope and glycoproteins

Question 3

2. Describe how HIV is transmitted.

Answer 3

sexual transmission, mother to child transmission (intrauterine, delivery and breast feeding), IV drug needle sharing, transfusion, transplantation, accidental sticks

(Blood, visibly blood body fluids, tissues, breast milk, semen and vaginal fluids are considered potentially infectious; additionally CSF, pleural, peritoneal, pericardial, synovial and amniotic fluids)

Question 4

3. Discuss how the virus disseminates throughout the immune system.

Answer 4

i. 48 hrs transport from site of exposure to lymph node, by dendritic cells
ii. infection of CD4+ T lymphocyte: requires CD4 receptor and CCR5 (early) or CXCR4 (later) chemokine co-receptor
iii. 4-11d dissemination: replication in regional lymph nodes, CNS, spleen, gut**
iv. 2-3 wks CD4+ depletion (80%) loss: GI tract lymph is largest reservoir of CD4+, important early hit

Question 5

3. Discuss how the virus evades the immune system.

Answer 5

1. genetic diversity of viral isolates evade humoral response; eventual decline of plasma viremia to viral load set point correlates with devo of HIV specific Ab
2. early and persistent loss of HIV specific CD4+ T lymphocytes
3. bacterial translocation across GI mucosa in part drives immune activation this chronic activation contributes to CV disease and cancer risk

Question 6

3. Discuss how the virus destroys the immune system.

Answer 6

vi. immune dysfunction: immune system loses coordination, increased opportunistic infection and malignancies; risk with intracellular (CMI) and also bacterial pathogens
1. lymphoid tissue architecture is distorted, impairing response
2. CD8+ T lymphocyte: quantitative and qualitative dysfunction
3. B cell dysregulation and hypergammaglobulinemia
4. NK cells are defective
5. Neutrophil dysfunction impaired opsonizing and increased apoptosis
6. Monocytes and macrophages: serve as reservoirs and role in CNS disease via microglia

Question 7

4. Discuss the various aspects of HIV immunopathogenesis.

Answer 7

a. Main components of HIV immunopathogenesis are transport from site of exposure to lymh node, infection of CD4+ T lymphs, dissemination, CD4+ lymph depletion, activation of immune system, complete immune dysfunction and latent reservoir

Question 8

5. Define the different stages of HIV infection.

Answer 8

a. Acute (primary) HIV infection: acute retroviral syndrome occurs (self-limited flu or mono like illness 2-6 weeks after infection and lasts 1-3 weeks)
b. Chronic asymptomatic infection: can last years, with progressive decline in CD4 counts and ongoing immune activation
c. Chronic symptomatic infection: nonspecific constitutional symptoms (weight loss, fatigue, generalized adenopathy, thrush, shingles, oral hairy leukoplakia, seborrhea dermatitis, psoriasis, HSV)
d. AIDS: CD4+ count <200/mm3 or the presence of certain AID indicator conditions (opportunistic infections and malignancies

Question 9

6. Discuss the laboratory tests used to diagnose HIV and AIDS.

Answer 9

a. Step #1 Highly sensitive screening test- Enzyme Immunoassay, continue if EIA reactive
b. Step #2 Highly specific confirmatory test- Western Blot, detects antibodies against specific viral proteins; window period time before HIV antibody is detectable 22d-6mo

c. 4th gen serologic testing methods combine serology with p24 antigen to improve detection of acute infection

Question 10

7. Distinguish acute (primary) HIV infection from acute infectious mononucleosis.

Answer 10

a. Rash can accompany HIV infection which is not typical of mono

Question 11

8. Explain how HIV can be prevented.

Answer 11

a. Access to testing and care, sexual abstinence, risk reduction sexual practices, barriers, needle exchange programs, ART for pregnant women, ART for potential exposure, testing blood products and tissues; treating to prevent spread, pre-exposure prophylaxis