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The lifecycle of HIV

  • HIV virions enter the bloodstream of a new host.
  • A protein on the surface of the virus – gp120 – has a high affinity for the CD4 receptor found on cells circulating in the blood called CD4+ or T helper cells.
  • When a virion encounters a CD4+ cell there is a reaction between gp120 and CD4, which attaches the virion to the host cell. This binding is strengthened further by a co-receptor on the cell surface. Disrupting these steps is the aim of antiretrovirals referred to as binding inhibitors, which are currently being developed.
  • Once the virion has been bound to the host cell surface, its next task is to get inside. This is achieved through the fusion of the virus coat and the cell membrane. Fusion inhibitors are being developed that prevent this step and so block the entry of HIV into its host cell.
  • Following fusion, the genetic material of the virus, which is RNA, is released into the cell, along with the viral enzymes, reverse transcriptase and integrase.
  • Reverse transcriptase reads the viral RNA and builds the corresponding DNA strands. The DNA copy is known as a provirus. Antiretroviral drugs belonging to the class of reverse transcriptase inhibitors work by blocking this conversion of RNA to DNA.
  • Viral DNA now moves to the cell nucleus, where the cell’s own genes, also made of DNA, are housed. Another viral enzyme, integrase, splices the strands of DNA into the host cell genome. Integrase is a potential target for future antiretrovirals.
  • Secure within the host cell’s genes, the proviral DNA can persist for many years in a latent state, secretly carrying the genetic instructions for making new virions.
  • When the host cell is activated – that is it begins to divide – the proviral DNA will be transcribed into RNA, which is then translated into viral proteins and polyproteins. Together, the RNA and these proteins then migrate to the inside of the host cell membrane, where they will be assembled into new virions.
  • Among the viral proteins is the enzyme, protease, which cleaves the polyproteins into smaller, functional proteins, thereby allowing the new viral particles to mature . Protease inhibitors are antiretrovirals that block the action of this enzyme and therefore prevent this essential step.
  • Following assembly, the newly formed virions bud from the host cell surface, entering the bloodstream where they will encounter uninfected CD4+ cells and begin another cycle.
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See also:
  What is HIV ?
  HIV is a retrovirus
  How is HIV transmitted ?
  Pathophysiology – how HIV causes disease
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