CD4-independent infection by HIV-2 is mediated by fusin/CXCR4

Cell. 1996 Nov 15;87(4):745-56. doi: 10.1016/s0092-8674(00)81393-8.


Several members of the chemokine receptor family have been shown to function in association with CD4 to permit HIV-1 entry and infection. However, the mechanism by which these molecules serve as CD4-associated cofactors is unclear. In the present report, we show that one member of this family, termed Fusin/ CXCR4, is able to function as an alternative receptor for some isolates of HIV-2 in the absence of CD4. This conclusion is supported by the finding that (1) CD4-independent infection by these viruses is inhibited by an anti-Fusin monoclonal antibody, (2) Fusin expression renders human and nonhuman CD4-negative cell lines sensitive to HIV-2-induced syncytium induction and/or infection, and (3) Fusin is selectively down-regulated from the cell surface following HIV-2 infection. The finding that one chemokine receptor can function as a primary viral receptor strongly suggests that the HIV envelope glycoprotein contains a binding site for these proteins and that differences in the affinity and/or the availability of this site can extend the host range of these viruses to include a number of CD4-negative cell types.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • B-Lymphocytes / virology
  • Base Sequence
  • CD4 Antigens / metabolism*
  • CHO Cells
  • Cell Fusion / drug effects
  • Cricetinae
  • Down-Regulation
  • Genetic Variation
  • HIV-2 / genetics
  • HIV-2 / growth & development*
  • Humans
  • Lymphocytes / virology*
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology
  • Membrane Proteins / metabolism*
  • Molecular Sequence Data
  • Quail
  • Receptors, CXCR4
  • Receptors, HIV / genetics
  • Receptors, HIV / immunology
  • Receptors, HIV / metabolism*
  • Recombinant Proteins / metabolism
  • T-Lymphocytes / virology


  • Antibodies, Monoclonal
  • CD4 Antigens
  • Membrane Proteins
  • Receptors, CXCR4
  • Receptors, HIV
  • Recombinant Proteins