title: 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.
abstract: 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia 19104, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Doranz
authors.forename: J
authors.initials: J
authors.lastname: Rucker
authors.forename: Y
authors.initials: Y
authors.lastname: Yi
authors.forename: R J
authors.initials: RJ
authors.lastname: Smyth
authors.forename: M
authors.initials: M
authors.lastname: Samson
authors.forename: S C
authors.initials: SC
authors.lastname: Peiper
authors.forename: M
authors.initials: M
authors.lastname: Parmentier
authors.forename: R G
authors.initials: RG
authors.lastname: Collman
authors.forename: R W
authors.initials: RW
authors.lastname: Doms
mesh_terms: 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
chemical_list: 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