The role of CD4 in HIV binding and entry

Philos Trans R Soc Lond B Biol Sci. 1993 Oct 29;342(1299):59-66. doi: 10.1098/rstb.1993.0136.


The primary cellular receptor for the human and simian immunodeficiency viruses HIV-1, HIV-2 and SIV is the CD4 antigen (Sattentau et al. 1988; Sattentau & Weiss 1988). HIV infection of CD4+ cells is initiated by binding of the virus to the cell surface, via a high-affinity interaction between the first domain of CD4 and the HIV outer envelope glycoprotein, gp120. The use of a soluble recombinant form of CD4 (sCD4) as a receptor mimic has simplified the analysis of receptor binding and post-binding events which result in virus-cell membrane fusion. With cell-line adapted isolates of HIV-1, sCD4 binding induces conformational changes in gp120, leading to the complete dissociation of gp120 from the transmembrane glycoprotein, gp41, and exposing cryptic epitopes of gp41. Similar observations have been made with cell-anchored CD4: recruitment of CD4 molecules leads to exposure of cryptic gp41 epitopes at the fusion interface between clusters of CD4 expressing and HIV-infected cells. It has therefore been proposed that CD4 binding induces exposure of fusogenic components of gp41 which mediate virus-cell membrane coalescence, a process termed receptor-mediated activation of fusion. With the related lentiviruses HIV-2 and SIV, the CD4 induced molecular rearrangements in gp120 are more subtle, implying that there is a spectrum of responses to sCD4 binding.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • CD4 Antigens / chemistry
  • CD4 Antigens / metabolism
  • CD4 Antigens / physiology*
  • Cell Fusion
  • HIV / physiology*
  • HIV Envelope Protein gp120 / metabolism*
  • HIV-1 / physiology
  • HIV-2 / physiology
  • Humans
  • Membrane Fusion
  • Models, Biological
  • Models, Structural
  • Simian Immunodeficiency Virus / physiology
  • T-Lymphocytes / physiology*


  • CD4 Antigens
  • HIV Envelope Protein gp120