HIV structure and replication cycle

HIV Structure - The Viral Blueprint

• Family: Retroviridae (a lentivirus).
• Core Components:
  • Envelope: Host-derived lipid membrane with viral glycoproteins.
    • gp120: Binds to the CD4 receptor on host cells.
    • gp41: Facilitates viral fusion and entry.
  • Capsid: Conical-shaped protein shell, p24.
  • Genome: Diploid; two identical single-stranded, positive-sense RNA strands.
  • Enzymes: 📌 Reverse Transcriptase, Integrase, Protease (RIP).

⭐ The p24 capsid protein is the first viral antigen to become detectable in the blood, making it a key marker for early HIV diagnosis.

HIV Tropism & Entry - Picking the Lock

• Initial Contact: HIV's envelope glycoprotein gp120 binds to the primary CD4 receptor on host cells (T-helper cells, macrophages).
• Coreceptor Binding (Tropism): This initial binding triggers a conformational change in gp120, allowing it to bind to a second coreceptor.
  • R5-Tropic (M-tropic): Uses CCR5 coreceptor, found on macrophages & memory T-cells. Dominant in early infection.
  • X4-Tropic (T-tropic): Uses CXCR4 coreceptor, on naive T-cells. Emerges in late-stage disease, linked to faster progression.
• Fusion & Entry: Coreceptor binding exposes gp41, which mediates fusion of the viral envelope with the host cell membrane, releasing the viral capsid inside.

⭐ Individuals homozygous for the CCR5-Δ32 mutation are highly resistant to R5-tropic HIV infection, as the virus cannot engage its coreceptor for entry.

📌 Mnemonic: gp120 knocks on the door (CD4), gp41 fuses the floor.

HIV Replication Cycle - Viral Hijacking

• Attachment, Penetration & Uncoating: Viral gp120 binds to the host T-cell CD4 receptor. A conformational change allows binding to a coreceptor, either CXCR4 (T-tropic) or CCR5 (M-tropic). Viral gp41 then mediates fusion and entry.

• Replication & Integration:

  • Reverse Transcription: Viral RNA is converted into dsDNA by reverse transcriptase (RNA-dependent DNA polymerase).
  • Integration: The new viral DNA is integrated into the host cell's genome by the enzyme integrase, forming a provirus.

• Synthesis, Assembly & Budding:

  • Host cell machinery transcribes the proviral DNA into mRNA.
  • Viral proteins and RNA assemble at the cell membrane.
  • The new virion buds off, and protease cleaves polyproteins into their functional forms, leading to maturation.

⭐ Exam Favorite: Individuals with a homozygous deletion of the CCR5 gene (CCR5-delta32 mutation) have resistance to HIV infection, as the virus cannot bind to and enter macrophages.

• HIV is a diploid, positive-sense, single-stranded RNA retrovirus.
• Key structural genes are env (gp120, gp41), gag (p24 capsid), and pol (reverse transcriptase, integrase, protease).
• Viral entry requires gp120 binding to CD4 and a co-receptor (CCR5 or CXCR4), followed by gp41-mediated fusion.
• Reverse transcriptase converts viral RNA into dsDNA, which is integrated into the host genome by integrase.
• Protease cleaves polyproteins during maturation, a key drug target.