Identification of c-c chemokine receptor 5 as the major coreceptor for entry of macrophage tropic human immunodeficiency virus type 1.
Int Conf AIDS 1996 Jul 7-12; 11:18 (abstract no. Th.A.927) Deng H, Liu R, Ellmeier W, Choe S, Unutmaz D, Burkhart M, Di Marzio P, Marmon S, Sutton RE, Hill CM, Davis CB, Peiper SC, Schall TJ, Littman DR, Landau NR; Aaron Diamond AIDS Research Centre, New York, NY. Fax: (212) 725-1126. E-mail: ned@adarc.nyu.edu.
Entry of HIV-1 into target cells requires cell surface CD4 as well as additional host cell cofactors. A cofactor required for infection with virus adapted for growth in transformed T cell lines was recently identified and named fusin. Fusin, however, does not promote entry of macrophage-tropic viruses that are believed to be the key pathogenic strains in vivo. We report here that the principal cofactor for entry mediated by the envelope glycoproteins of primary macrophage-tropic strains of HIV-1 is CC-CKR-5, a receptor for the beta-chemokines RANTES, MIP-1alpha and MIP-1beta. These findings provide insight into the basis of Env-controlled tropism, the mechanism by which HIV-1 enters susceptible cells and the mechanism by which beta-chemokines inhibit replication of macrophage-tropic HIV-1. We speculate that the basis of the phenotypic switch that occurs in some infected individuals late in the disease is the result of a switch in coreceptor usage from CC-CKR-5 to fusin.
Keywords: AEGIS, Chemokines, CC, HIV-1, Receptors, CXCR4, Macrophages, RANTES, Macrophage Inflammatory Protein-1, Antigens, CD4, Virus Replication, Carrier Proteins, Human, virology, ICA11
