Chemokine receptors as fusion cofactors for human immunodeficiency virus type 1 (HIV-1).
CD4 is the primary cellular receptor for human immunodeficiency virus type 1 (HIV-1), but is not sufficient for entry of HIV-1 into cells. After a decade-long search, the cellular coreceptors that HIV-1 requires in conjunction with CD4 have been identified as members of the chemokine receptor family of seven-transmembrane G-protein coupled receptors. The discovery of distinct chemokine receptors that support entry of T-cell tropic (CXCR-4) and macrophage tropic HIV-1 strains (CCR-5) explains the differences in cell tropism between viral strains, the inability of HIV-1 to infect most nonprimate cells, and the resistance of a small percentage of the population to HIV-1 infection. Further understanding of the role of chemokine receptors in viral entry may also help explain the evolution of more pathogenic forms of the virus, viral transmission, and HIV-induced pathogenesis. These recent discoveries will aid the development of strategies for combating HIV-1 transmission and spread, the understanding of HIV-1 fusion mechanisms, and the possible development of small animal models for HIV-1 drug and vaccine testing.
Doranz
B J
BJ
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia 19104, USA.
Berson
J F
JF
Rucker
J
J
Doms
R W
RW
D015704:CD4 Antigens; D018925:Chemokines / Q000276:immunology / Q000502:physiology*; D015497:HIV-1 / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D008561:Membrane Fusion; D008565:Membrane Proteins; D011110:Polymorphism, Genetic / Q000276:immunology; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D018121:Receptors, Cytokine / Q000502:physiology*; D015728:Receptors, HIV / Q000502:physiology*
D015704:CD4 Antigens; D018925:Chemokines; D008565:Membrane Proteins; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D018121:Receptors, Cytokine; D015728:Receptors, HIV