Viruses (HIV)

Viruses (HIV)

1. Anti-retroviral therapy

   • Entry inhibitors
     • Inhibits fusion and blocks co-receptor
     • Enfuvirtide, Maraviroc
   • RT inhibitors
     • NRTIs
       • nucleoside analogues
       • prevents DNA chain formation
     • NNRTIs
       • changes RT binding site shape
       • Nevirapine, efavirenz, etravirine
   • Integrase inhibitors
     • prevents integration of viral dsDNA to host DNA
     • Raltegravir, elvitegravir, dolutegravir
   • Protease inhibitors
     • inhibit HIV asaprtyl protease
     • Saquinavir, indinavir, nelfinavir, ritonavir (booster)

2. Life Cycle

   • Binding/Attachment
     • HIV binds to CD4
   • Fusion
     • HIV envelope and cell membrane fuse
     • HIV enters
   • Reverse Transcription
     • RT converts HIV RNA to HIV DNA
   • Replication
     • HIV forms protein chains
   • Integration
     • Integrase inserts viral DNA into CD4 cell's DNA
     • In host cell nucleus
   • Assembly
     • new viral proteins + HIV RNA assemble
   • Budding
     • Immature HIV leaves host cell
     • Protease cleaves protein chains to make it mature

3. Natural History

   • 1. Primary infection
     • Acute / Flu-like symptoms
   • 2. Clinical latency
     • 8-10 years (without ART)
     • Asymptomatic
     • Still transmissible
   • 3. AIDS
     • AIDS-related cancers

4. Structure

   • positive sense ssRNA
   • Enveloped icosahedral
   • Retrovirus

5. Tests

   • Blood sample
     • Viral load
     • CD4 count
     • Antigen - p24
   • ELISA
     • False negative
       • Window period
   • Western Blot
     • Confirmatory

6. Immune Response

   • Spreads to lymphoid tissue
   • HIV production enhanced by microbes' cytokines
   • Loss of CD4 T cells
     • Killed by antigen-specific CTL
     • Pyroptosis
     • Thymus impairment
   • CD4 increases slightly during viral latency
   • HIV-specific CTL decreases as viral load increases
     • CTL may become exhausted
   • Immune evasion
     • Antigenic variation
     • Inhibit IFN production
     • Inhibit complement activation
     • Impair/kill immune cells

7. Risk Factors/Transmission

   • Sexual contact
     • Unprotected sex
   • Parenteral
     • Needle sharing
     • Blood-borne
   • Mother to child
     • Before/during birth
     • Breastfeeding

8. Mechanism of Action

   • attaches to t-cells by CD4
     • Co-receptors: CCR5, CXCR4
     • HIV increases = CD4 decreases
       • < 500 = infection risk
       • <=200 = AIDS
   • Glycoproteins: gp120, gp41

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