Regions in beta-chemokine receptors CCR5 and CCR2b that determine HIV-1 cofactor specificity

Cell. 1996 Nov 1;87(3):437-46. doi: 10.1016/s0092-8674(00)81364-1.


Macrophage-tropic (M-tropic) HIV-1 strains use the beta-chemokine receptor CCR5, but not CCR2b, as a cofactor for membrane fusion and infection, while the dual-tropic strain 89.6 uses both. CCR5/2b chimeras and mutants were used to map regions of CCR5 important for cofactor function and specificity. M-tropic strains required either the amino-terminal domain or the first extracellular loop of CCR5. A CCR2b chimera containing the first 20 N-terminal residues of CCR5 supported M-tropic envelope protein fusion. Amino-terminal truncations of CCR5/CCR2b chimeras indicated that residues 2-5 are important for M-tropic viruses, while 89.6 is dependent on residues 6-9. The identification of multiple functionally important regions in CCR5, coupled with differences in how CCR5 is used by M- and dual-tropic viruses, suggests that interactions between HIV-1 and entry cofactors are conformationally complex.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • CD4 Antigens / physiology
  • Cytopathogenic Effect, Viral
  • Glycosylation
  • HIV-1 / physiology*
  • HeLa Cells
  • Humans
  • Macromolecular Substances
  • Macrophages / virology
  • Membrane Fusion
  • Molecular Sequence Data
  • Protein Conformation*
  • Protein Processing, Post-Translational
  • Receptors, CCR2
  • Receptors, CCR5
  • Receptors, Chemokine*
  • Receptors, Cytokine / chemistry*
  • Receptors, Cytokine / physiology
  • Receptors, HIV / chemistry*
  • Receptors, HIV / physiology
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Sequence Deletion
  • Structure-Activity Relationship


  • CCR2 protein, human
  • CD4 Antigens
  • Macromolecular Substances
  • Receptors, CCR2
  • Receptors, CCR5
  • Receptors, Chemokine
  • Receptors, Cytokine
  • Receptors, HIV
  • Recombinant Fusion Proteins