Lecture #167: Microbiology: HIV and Retroviruses

What virus is the origin of HIV-1?

Simian immunodeficiency virus (SIV), specifically SIVcpz, which crossed into humans via zoonotic transmission.

What is the earliest documented case of HIV?

A blood sample from 1959 in Kinshasa, Democratic Republic of Congo.

What family does HIV belong to?

Retroviridae, which includes HIV-1, HIV-2, and HTLV viruses.

What type of genome does HIV have?

Two copies of single-stranded RNA (ssRNA).

What enzyme converts HIV RNA to DNA?

Reverse transcriptase converts viral RNA into double-stranded DNA.

What does integrase do in HIV?

Inserts viral DNA into the host genome to form a provirus.

What is the function of HIV protease?

Cleaves viral polyproteins (gag and pol) into functional proteins during maturation.

What does gp120 do?

Binds to CD4 receptors and co-receptors (CCR5 or CXCR4) on host cells.

What does gp41 do?

Facilitates fusion of the viral envelope with the host cell membrane.

What cells does HIV primarily infect?

CD4+ T helper cells, macrophages, and dendritic cells.

What co-receptors are used by HIV?

CCR5 (early infection) and CXCR4 (later infection).

What is the mechanism of HIV entry?

gp120 binds CD4 and co-receptor → gp41 mediates membrane fusion → viral entry.

What is the HIV life cycle sequence?

Attachment, fusion, reverse transcription, integration, transcription, translation, assembly, budding, maturation.

What is the role of gag gene?

Encodes structural proteins such as p24 (capsid) and p17 (matrix).

What is the role of pol gene?

Encodes reverse transcriptase, integrase, and protease.

What is the role of env gene?

Encodes envelope proteins gp120 and gp41.

What is Nef protein function?

Downregulates CD4 and MHC I, helping immune evasion.

What is Rev protein function?

Facilitates export of viral RNA from nucleus.

What is Vif protein function?

Degrades host antiviral protein APOBEC3G.

What is the most common route of HIV transmission in the U.S.?

Sexual contact, especially among men who have sex with men.

What increases HIV transmission risk?

Presence of genital ulcerative STIs increases risk up to 5-fold.

What are non-transmission routes of HIV?

Not spread by saliva, tears, sweat, casual contact, or insects.

What is acute retroviral syndrome?

Early symptomatic phase 2–4 weeks after infection with flu-like illness.

What are symptoms of acute HIV infection?

Fever, lymphadenopathy, rash, pharyngitis, headache, diarrhea.

How long does acute HIV illness last?

Typically 2–6 weeks with possible prolonged fatigue.

What is clinical latency in HIV?

Asymptomatic phase with ongoing viral replication and gradual CD4 decline.

What is the average time to symptomatic HIV without treatment?

About 8–10 years.

What CD4 count defines AIDS?

CD4 <200 cells/μL or presence of AIDS-defining illness.

What happens at CD4 <200?

Severe immune dysfunction with high risk of opportunistic infections.

What are common opportunistic infections in AIDS?

Pneumocystis jirovecii pneumonia, toxoplasmosis, CMV retinitis, MAC.

What cancers are associated with HIV/AIDS?

Kaposi sarcoma, cervical cancer, CNS lymphoma.

What is HIV viral load?

Measure of HIV RNA in blood indicating disease progression and treatment response.

What does high viral load indicate?

Increased risk of disease progression and mortality.

What is the goal of ART?

Suppress viral load to undetectable levels and restore immune function.

What happens with undetectable viral load?

Near-normal lifespan and no sexual transmission (U=U).

What is first-line ART regimen?

Combination therapy typically including integrase inhibitor + 2 NRTIs.

What is example of ART combination?

Bictegravir, emtricitabine, and tenofovir alafenamide.

What is maraviroc mechanism?

CCR5 antagonist blocking viral entry.

What is enfuvirtide mechanism?

Inhibits gp41-mediated membrane fusion.

What do NRTIs do?

Act as false nucleosides to inhibit reverse transcriptase.

What do NNRTIs do?

Inhibit reverse transcriptase enzyme directly.

What do protease inhibitors do?

Prevent viral maturation by inhibiting protease.

What do integrase inhibitors do?

Block integration of viral DNA into host genome.

What test is used to diagnose HIV initially?

4th generation HIV antigen/antibody assay (detects p24 and antibodies).

What test confirms early HIV if initial test negative?

HIV RNA viral load testing.

What labs are ordered in new HIV diagnosis?

CD4 count, viral load, resistance testing, STI screening, hepatitis panel.

What prophylaxis is given at CD4 <200?

TMP-SMX for Pneumocystis jirovecii pneumonia.

What is PrEP?

Pre-exposure prophylaxis that significantly reduces risk of acquiring HIV.

What is PEP?

Post-exposure prophylaxis started after potential HIV exposure.

Is there a cure for HIV?

No cure currently, but ART allows long-term control of infection.

What is long-acting HIV therapy option?

Monthly injectable cabotegravir and rilpivirine for maintenance therapy.