HIV Life Cycle and Inherited Co‐receptors

Michael I Bukrinsky, The George Washington University, Washington, DC, USA

Published online: December 2010

DOI: 10.1002/9780470015902.a0002240.pub3

‘Human immunodeficiency virus’ (HIV) is a Lentivirus of the family Retroviridae, members of which cause a number of neurological and immunological diseases in humans and animals. HIV is the causative agent of the acquired immune deficiency syndrome (AIDS). The disease is caused by virus-mediated depletion of CD4+ T lymphocytes, preferentially CCR5-positive memory T cells. Most of these cells localise to mucosal tissue, in particular gut mucosa, and disruption of the gut mucosal barrier is an early feature of HIV infection that determines the pathogenesis of the disease. More than 20 years of intensive studies identified the molecular mechanisms underlying viral replication and disease pathogenesis, and provided the foundation for development of antiviral therapeutics and vaccine. This article provides a brief overview of the HIV life cycle and focuses on receptors that determine viral binding and entry into the target cells.

Key Concepts:

  • Virus–cell interaction is initiated by interaction between gp120 and target cell receptors.
  • HIV preferentially targets memory CD4+ T cells which localise to mucosal lymphoid tissue, in particular the gut mucosa.
  • HIV replication includes a number of distinct steps: virus–cell fusion and viral entry; viral uncoating; viral reverse transcription and formation of the pre-integration complex (PIC); PIC nuclear entry and integration; viral transcription and translation; viral assembly and release of nascent virions; viral.
  • Characterisation of the molecular mechanisms underlying HIV replication and interaction with the target cells provides an opportunity to develop anti-HIV therapeutics and vaccine.

Keywords: Lentivirus; macrophage; T lymphocyte; dendritic cell; CD4; chemokine receptor; integrin; lectin

Figure 1. Composition of HIV-1. Viral bilayer membrane is derived from cellular plasma membrane. Each knob is composed of three gp120 molecules noncovalently associated with a stem made of a gp41 trimer. Matrix antigen (MA) forms a layer beneath the envelope. The shell of the viral core is made of capsid antigen (CA). Only a few of the several hundred copies of integrase (IN), reverse transcriptase (RT), nucleocapsid (NC) and viral protein R (Vpr) molecules are shown. Vpr associates tightly with Gag p6, and RT most likely contacts IN. Not drawn to scale. Details are discussed in the text.
Figure 2. HIV-1 co-receptors. Human immunodeficiency virus 1 (HIV-1) interacts with its receptors via the envelope protein, gp120, which binds to the D1 immunoglobulin-like domain of CD4 and the extracellular domain of a chemokine receptor. Chemokines bind to extracellular loop 2 (ECL-2) on the chemokine receptor. However, interaction between gp120 and ECL-2 is required for virus–cell fusion and likely occurs shortly after initial binding interaction; therefore, gp120 inhibits binding of chemokines to receptor, whereas chemokines block virus–cell fusion and HIV-1 infection. Both gp120 and chemokines initiate signal transduction through chemokine receptor coupled Gi protein, but gp120 can also signal through CD4-associated Src kinase, p56lck. ICL, intracellular loop.
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Related Sub-Topics:

Virus Diseases | Viruses Infecting Humans | RNA Viruses | Virus Replication
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Article Title: HIV Life Cycle and Inherited Co‐receptors
 
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Bukrinsky, Michael I(Dec 2010) HIV Life Cycle and Inherited Co‐receptors. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0002240.pub3]