Microbiology Exam 2 Essay - HIV Questions

a)  Signs and Symptoms of the disease – Lecture 7, Slides 13, 14, 15, 16 – Describe four stages of HIV infection, including: Duration, Signs and Symptoms, Immune response

·      First – Incubation period (2 – 4 wks): NO S/S; NO immune response

·      Second – Acute HIV infection (≤ 1 month): S/S fever, swollen lymph nodes, pharyngitis, thrush, weight loss, drop in T helper-cells (CD4) from 1200 cells/µL to 800 cells/µL; Immune response HIV antibodies produced → virus opsonized, infected T cells destroyed → macrophages newly infected b/c virus avoids formation of phagolysosome

·      Third – Latency stage (2 wks – 20 yrs) S/S mild or non-existant; Immune response HIV eliminated from blood stream, hiding in macrophages + increasing through budding → new virions infect T helper-cells → infected T helper-cells killed = drop in T cell count

·      Forth – AIDS (~1 month) T helper-cell count < 200 cells/µL S/S Depends on types of opportunistic infections examples Pneumocystis pneumonia, Candidiasis, Kaposi’s sarcoma; Immune response immunodeficiency

b)  Etiological agent of the disease – Lecture 7, Slides 17, 18, 19, 20 – Describe the 
following: Structure of the virus & Functions of two major proteins of viral envelop; Functions
of three viral enzymes included in capsid. Replication of HIV in host cell

·      Enveloped retrovirus, capsid w/ 2x ss(+) RNA genome + 3 viral enzymes

·      Two major viral envelope proteins: gp 120 (receptor/docking protein – CD4 + CXCR4 coreceptor) and gp 41 (transmembrane protein)

·      3 viral enzymes: reverse transcriptase (ssRNA → dsDNA), integrase (viral dsDNA integrated into host cell chromosome), protease (cleave new non-active viral proteins → active)

·      HIV replication: (1) Attachment and entry – gp120 docking protein attaches to host T_H cells through CD4 and CXCR4 or CCR5(macrophages) → Viral envelope fuses w/ host cell membrane →  virus uncoats releasing genetic material →  (2) Provirus – ssRNA → dsDNA w/ reverse transcriptase → new viral DNA integrated into host cell’s chromosomes w/ integrase → (3) Replication of virus – Viral genes expressed and producing new virions → HIV release via budding

c)  Pathogenesis of the disease – Lecture7,Slides19,21,22 – Describe: Damage done by HIV to the host; Why macrophages become HIV reservoir in 
infected person; HIV diagnostics

·      HIV infection kills off T helper-cells b/c body’s NK cells and compliment system attacks infected T_H cells

·      Macrophages are persistent reservoir for HIV: Anti-HIV antibodies opsonize HIV for macrophages to phagocytize them → HIV inhibits fusion of phagosome and lysosome → virus escapes phagosome and undergoes viral replication cycle → provirus

·      T_H cells reduced over time, < 200 cells/µL (AIDS) = immune system fails to mount immune response to infection.

·      Diagnostic: Genetic analysis (PCR reaction), Serological analysis (Western blot – HIV antigens present in serum only in acute and AIDS, NOT latent stage) OR (ELISA – Search for anti-HIV antibodies)

d)  Epidemiology of the disease – Lecture 7, Slides 23, 24, 25, 26; 27 – Origin, Reservoir, Routes of transmission of HIV infection. US statistical data for 2011

·      Originated in chimpanzees → transferred through hunting primates for bush meat (~late 19^th or early 20^th century) → Until 1950s endemic to certain areas on Africa → Oldest known case of AIDS in 1959 Congo → development of modern transport + unsafe sex spreads HIV → 1976 1^st Westerner (Norwegian sailor) dies from AIDS

·      Reservoir:  Human blood, breast milk, semen (can survive for up to 6 hrs)

·      Transmission: Sexual contact (Homo + hetero), injected drug use, blood transfusion, inborn, transplant, breast milk

·      US stats 2011 – 40,000+ cases of new HIV infections reported, 64% homo, 28% hetero, 8% injected, other route < 1%. Most new cases from 20-35 age range. NY 4^th in # of new cases (~5000). African Americans + White have same cumulative # of HIV cases.

e)  Prevention and Treatment of the disease – Lecture 7, Slides 28, 29, 30 – Prevention of HIV infection; Treatment of HIV; Cost and availability of retroviral drugs to HIV-infected world-wide

·      Prevention: Use of condoms (reduce trauma to mucous membrane), sterile needles, healthcare PPE, Antiretroviral therapy upon accidental exposure, mandatory blood screening.
NO vaccines yet. All are in clinical trails

·      Treatment: Reverse transcriptase inhibitors (didanosone, nevirapine, delavirdine), integrase inhibitors, protease inhibitors (Indinavir, ritonavir)