HIV Structure and Genes Overview

HIV Structure

• HIV-1 virion is spherical, composed of an electron-dense, cone-shaped core enclosed by a lipid envelope derived from the host cell membrane.
• Genes essential to viral replication:
  • TAT gene: Enhances the transcription and expression of viral proteins by binding to the TAR.
  • REV gene: Post transcriptional activator for splicing and transportation of viral mRNA (production of structural proteins)
  • LTR sequence: Promoter and enhancer elements
  • gag gene: Codes for the group-specific antigen
  • pol gene: Codes for reverse transcriptase, protease, and integrase
  • env gene: Codes for the envelope glycoprotein (gp)
• Genes not essential to viral replication (but enhance the capacity of the virus to survive):
  • Virus infection factor (vif): Makes the virus more infectious
  • Negative factor (nef): Inhibits or activates viral transcription as required, influences t cell activation, reduces CD4 expression
  • vpr: Controls the rate of replication
  • vpx: Specific to HIV 2, controls the rate of replication
  • vpu: Specific to HIV 1, contributes to viral release, increases CD4 turnover.

HIV Transmission

• Can be transmitted through:
  • Intimate sexual contact:
    • 85% of transmissions are through heterosexual contact worldwide.
    • Transmission is more likely when STIs are present because of lesions in the genitals.
  • Contact with blood or other body fluids:
    • Sharing of contaminated needles.
    • Average risk of transmission to healthcare workers:
      • 0.3% percutaneous exposure (needle stick).
      • 0.09% mucous membrane exposure.
  • Perinatally, infected mother to infant (vertical transmission).
  • Saliva is assumed to have a low risk of transmission.

HIV Binding and Fusion

• gp120 (HIV) binds to CD4 T cells (T tropic/X4 strains) and other cells (M tropic/R5 strains): macrophages, monocytes, dendritic cells, Langerhans cells and microglial cells.
• Fusion:
  • Requires chemokine receptors:
    • CXCR4: For T-cells
    • CCR5: For macrophages
  • Occurs when chemokine receptor binds to gp120 and gp41

Reverse Transcription

• HIV capside: Bullet shaped core that contains HIV RNA
• HIV envelope: Outer surface of HIV
• HIV enzymes: Proteins that carry out steps in the HIV life cycle
• HIV glycoproteins: Protein spikes on HIV envelope
• HIV RNA: HIV's genetic material
• Viral contents gain entry to the host membrane.
• HIV RNA unravels followed by reverse transcription.
• Enzyme reverse transcriptase produces complementary DNA (cDNA) from the viral RNA.

Stages of HIV Infection

• Acute infection stage/primary HIV infection:
  • Flu-like symptoms: fever, swollen glands, sore throat, rash, muscle and joint pains, fatigue, headache.
• Clinical latency stage/chronic HIV infection: Asymptomatic HIV infection
• AIDS (terminal stage):
  • CD4+ cells fall below 200 cells/mm3.
  • RNA copies rise.
  • One or more opportunistic illnesses develop, regardless of CD4 count (AIDS defining disease).

Diagnostic Definitions of AIDS

• Adults:
  • Serves as a clinical diagnosis.
  • Table 5. Categories of AIDS:
    • CD4+ T cells/ul | Clinical Categories

    • 500 | A1 | B1 | C1

    • 200-499 | A2 | B2 | C2
• Data shows the majority of cases are in individuals aged 25-34 years old.
• Minimal risk of transmission in pregnant women, but children can be infected at birth.

Serodiagnosis of HIV

• Diagnostic definition:
  • Signals are interpreted by the machine.
  • Removing erythrocytes by lysis.
  • Stabilizing leukocytes by fixation with paraformaldehyde.
  • Normal: 600-1200 cells/uL