Human Immunodeficiency Virus

Human Immunodeficiency Virus (HIV)

HIV is a zoonosis resulting from cross-species transmission of Simian Immunodeficiency Virus (SIV) from monkeys

HIV taxonomy

Retroviridae othoretrovirinae lentivirius

HIV structure

• Positive single stranded RNA with 2 copies

• Enveloped

• Conical capsid core

HIV genomes

Gag (structural), pol (enzymes like reverse transcriptase and protease), and env (envelope)

HIV multiplication cycle

1. Binding and entry

2. Reverse transcription

3. Integration: insertion of the viral DNA to the host DNA

4. Replication and transcription

5. Assembly and budding

6. Maturation

HIV variability

Replicates rapidly with a low-fidelity reverse transcriptase → frequent errors → high diversity

Viral recombination

Exchange of fragments of genetic material (DNA or RNA) among parental viral genome

HIV-1 diversity

• Group M (major): europe, america, australia

• Group O (outlier): central africa

• Group N: cameroon

• Group P: cameroon

HIV-2 diversity

A (sub-groups A1 and A2), B, C, D, E, F, G, H, and I

Viral quasispecies

Population structure of viruses with a large number of variant genomes

HIV envelope glycoproteins

• gp120 and gp41 for HIV-1

• gp105 and gp36 for HIV-2

HIV-2 infection and treatment

HIV-2 progresses more slowly and has a lower transmission risk but is naturally resistant to certain classes of antiretrovirals

HIV modes of transmission

• Sexual route

• By blood

• From mother ro child: pregnancy, childbirth and breastfeeding

HIV target cells

CD4 T lymphocytes

HIV receptors

CD4 receptor and coreceptors (CCR5 or CXCR4) to enter cells

CCR5 polymorphism

• Level of expression varies from one individual to another

• CCR5△32 → protect R5 infections

HIV natural infection

Progresses from primary infection (high viral load) to clinical latency (stable but declining CD4 count) and finally to AIDS (acquired immunodeficiency syndrome)

Establishment of HIV infection

Virus spreads rapidly in the body

1. Initially interacts with dendritic cells

2. Reach the blood (CD4 T lymphocytes) in 4 to 6 hours

3. Reach the lymph nodes in 48 hours

4. Detectable in the blood in 4 to 11 days

5. HIV antibodies can be detected after 1 month

HIV reservoir

• The viral load reappears when the antiretroviral therapy (HAART) is stopped

• CNS, lymph nodes, lymphoid tissue associated with digestive tissue, bone marrow, genital tract, blood, spleen, fatty tissue, lung

• HIV can persist in this latent state as long as the cell carrying it

Evolution of HIV Infection

Progressive destruction of CD4 T lymphocytes

HIV symtoms

• acute viral syndrome

• polyadenopathy

• cutaneous-mucous manifestations

• digestive disorders

• neurological symptoms

• hepatic cytolysis

HIV CD4 T lymphocyte rate

• Following initial contamination, there is often a long period where no apparent signs of the disease are visible, though the CD4 count is steadily decreasing.

• Reappearance of Symptoms: As the CD4 rate falls below 500 cells/mm³, clinical manifestations begin to (re)appear as the immune system weakens

HIV CDC classification

• A: asymptomatic phase

• B: symptomatic (non-AIDS)

• C: AIDS (opportunistic infections)