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.
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.
Doranz
B J
BJ
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia 19104, USA.
Rucker
J
J
Yi
Y
Y
Smyth
R J
RJ
Samson
M
M
Peiper
S C
SC
Parmentier
M
M
Collman
R G
RG
Doms
R W
RW
D000163:Acquired Immunodeficiency Syndrome / Q000821:virology; D001483:Base Sequence; D002459:Cell Fusion / Q000502:physiology*; D018925:Chemokines / Q000502:physiology; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells / Q000502:physiology / Q000821:virology; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology*; D008969:Molecular Sequence Data; D010641:Phenotype; D054397:Receptors, CCR3; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000502:physiology*; D015728:Receptors, HIV / Q000502:physiology*; D014759:Viral Envelope Proteins / Q000235:genetics
C515350:CCR3 protein, human; D018925:Chemokines; D008565:Membrane Proteins; D054397:Receptors, CCR3; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D015728:Receptors, HIV; D014759:Viral Envelope Proteins