A dual-tropic primary HIV-1 isolate that uses fusin and the beta-chemokine receptors CKR-5, CKR-3, and CKR-2b as fusion cofactors

Cell. 1996 Jun 28;85(7):1149-58. doi: 10.1016/s0092-8674(00)81314-8.


Here, we show that the beta-chemokine receptor CKR-5 serves as a cofactor for M-tropic HIV viruses. Expression of CKR-5 with CD4 enables nonpermissive cells to form syncytia with cells expressing M-tropic, but not T-tropic, HIV-1 env proteins. Expression of CKR-5 and CD4 enables entry of a M-tropic, but not a T-tropic, virus strain. A dual-tropic primary HIV-1 isolate (89.6) utilizes both Fusin and CKR-5 as entry cofactors. Cells expressing the 89.6 env protein form syncytia with QT6 cells expressing CD4 and either Fusin or CKR-5. The beta-chemokine receptors CKR-3 and CKR-2b support HIV-1 89.6 env-mediated syncytia formation but do not support fusion by any of the T-tropic or M-tropic strains tested. Our results suggest that the T-tropic viruses characteristic of disease progression may evolve from purely M-tropic viruses prevalent early in virus infection through changes in the env protein that enable the virus to use multiple entry cofactors.

Publication types

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

MeSH terms

  • Acquired Immunodeficiency Syndrome / virology
  • Base Sequence
  • Cell Fusion / physiology*
  • Chemokines / physiology
  • HIV-1 / physiology*
  • HeLa Cells / physiology
  • HeLa Cells / virology
  • Humans
  • Membrane Proteins / physiology*
  • Molecular Sequence Data
  • Phenotype
  • Receptors, CCR3
  • Receptors, CCR5
  • Receptors, CXCR4
  • Receptors, Chemokine*
  • Receptors, Cytokine / physiology*
  • Receptors, HIV / physiology*
  • Viral Envelope Proteins / genetics


  • CCR3 protein, human
  • Chemokines
  • Membrane Proteins
  • Receptors, CCR3
  • Receptors, CCR5
  • Receptors, CXCR4
  • Receptors, Chemokine
  • Receptors, Cytokine
  • Receptors, HIV
  • Viral Envelope Proteins