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HIV Microbiology

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Summary

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Key Points

  • Human Immunodeficiency Virus (HIV) (FA 2019 p170)
    • Characteristics
      • Lentivirus of the Retrovirus family
      • Diploid genome (2 molecules of RNA)
      • 3 structural genes
        • env (“Envelope”)
          • Encoded polypeptide glycosylated to form glycoprotein 160 (gp160), which is cleaved to produce:
            • gp120
              • Mediates attachment to host CD4+ T cell
              • Binds CD4 as well as a chemokine coreceptor
                • CCR5 on macrophages (early infection)
                  • Homozygous CCR5 mutation = resistance to infection
                  • Heterozygous CCR5 mutation = slower course (delayed infection)
                  • CCR5 antagonists (maraviroc) block attachment by HIV
                • CXCR4 on T cells (late infection)
            • Gp41
              • Mediates fusion/entry into host cell
              • Targeted by “fusion inhibitors”, which prevent viral fusion with target cell membrane (e.g. enfuvirtide)
        • gag  (“Group specific antigen”)
          • p24 - capsid protein
          • p17 - matrix protein
        • pol  (“Polymerase”)
          • Reverse transcriptase
            • Synthesizes dsDNA from genomic RNA template
              • RNA-dependent DNA polymerase
                • Converts RNA into cDNA
              • dsDNA (provirus) then integrates into the host genome (see Integrase below)
            • Targeted by reverse transcriptase inhibitors
              • NRTIs = zidovudine, emtricitabine, abacavir, lamivudine
                • Most need to be phosphorylated to function
              • NNRTIs = nevirapine, efavirenz
                • Do not need phosphorylation
          • Integrase
            • Integrates HIV genome (DNA from reverse transcription) into host cell’s chromosome
            • Targeted by integrase inhibitors (e.g. Raltegravir, dolutegravir)
          • Protease
            • Most proteins needed for HIV replication are translated into a polyprotein precursor, which is cleaved into individual proteins by proteases
            • Targeted by protease inhibitors (e.g. saquinavir, atazanavir, indinavir, darunavir)