HIV: Microbiology and Characteristics

Summary

HIV stands for human immunodeficiency virus, and it infects immune cells to cause a weakened immune system in people. It uses RNA as its genetic material, and is diploid because it contains two copies of its RNA. There are three key genes to know for HIV. 

The first is the env gene. Env encodes two proteins - gp120 and gp41. Gp120 helps HIV attach to host cells by binding to co-receptors CCR5 and CXCR4. After binding, gp41 helps HIV fuse with and enter the host cell.

The second gene is the gag gene. Gag also encodes two proteins. The first is p24, which is a capsid protein. The second is p17, which is a matrix protein.

The third and final gene is the pol gene. Pol encode three important enzymes that help HIV replicate. The first is reverse transcriptase, which converts HIV’s RNA to DNA. The second is integrase, which integrates or inserts the newly made DNA into the host cell’s DNA. Finally, protease comes in and cleaves the protein precursors produced by host cell machinery into functional proteins necessary for successful virus replication.

Key Points

• Human Immunodeficiency Virus (HIV)
  • 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 two products below
      • 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
          • Reverse direction of central dogma (hence: “reverse transcription”)
          • 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)