Understanding HIV Infection in Lymph Nodes

Aug 25, 2024

HIV Infection in Lymph Nodes

Overview

  • HIV is brought to lymph nodes by dendritic cells or macrophages.
  • Infects T helper cells (CD4 lymphocytes).
  • CD4 cell count is <200 cell/mm -HIV can mimic mononucleosis (fever, HA, sore throat, lymphadenopathy, rash, joint ache, myalgia) and my be accompanied by diarrhea and weight loss.

Key Receptors

  • CD4 Receptor: Primary receptor required for HIV to bind to T helper cells
  • Co-receptors: CCR5 (preferred) and CXCR4.

HIV Entry Mechanism

  • Gp120 Protein on HIV envelope binds CD4 receptor. Lock (CD4) and key (Gp120) receptors.
  • Induces conformational change in CD4, allowing CCR5/CXCR4 to pull viral and T cell membranes together. The CD4, CCRS receptor pulls the viral membrane closer to bind
  • Gp120 protein stalk pierces T cell membrane, pulling the two closer together fusing the membranes.
  • HIV injects its genetic material (viral RNA) into T cell.

Viral RNA to DNA Conversion

  • Reverse Transcriptase: Converts viral RNA into single-stranded DNA, then into double-stranded DNA.
    • High error rate leads to mutations, complicating vaccine development.

Integration into Host DNA

  • Integrase Enzyme: Integrates viral DNA is carried into T cell nucleus then cuts or snips a section in the DNA to integrate itself into the persons DNA.
    • Either remains latent or the DNA transcribed into mRNA.

HIV Replication and Budding

  • Viral mRNA leads to creation of new viral proteins.
  • Polyproteins: Long protein strands including viral enzymes (reverse transcriptase, integrase).
  • Protease enzyme: Cleaves polyproteins into functional viral components.
  • New virions bud off T cell, becoming mature HIV particles.

T Helper Cell Death

  • Not due to budding off virions.
  • Often due to self-destruct mechanism triggered by HIV production.

Implications

  • High mutation rate from reverse transcriptase hinders medication and vaccine development.
  • Chronic infection as viral DNA integrates into host DNA.