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

This quiz covers the essential structure of the HIV-1 virion and key genes involved in its replication. Explore the roles of the TAT, REV, LTR, gag, pol, and env genes, along with additional factors that enhance the virus's survivability. Test your knowledge on the molecular biology of HIV.