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Background
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Human immunodeficiency virus (HIV-1) and related viruses such as HIV-2 and SIV require coreceptors to infect target cells. The G protein-coupled receptors CCR3, CCR5 and CXCR4 are the principal receptors for HIV fusion and entry of target cells. CCR3 and CCR5 promote efficient infection of microglia, the major target cells in the CNS. Eotaxin, the CCR3 ligand and an anti-CCR3 antibody inhibited HIV infection of microglia. CCR5 is a principal coreceptor for macrophage- and dual-tropic HIV-1 strains fusion and entry of human white blood cells. The amino-terminal domain and the extracellular loops of CCR5 serve as HIV biding sites. High levels of CCR3 and CXCR4 expression were found on the neurons from both the central and peripheral nervous systems. CXCR4 is a principal coreceptor for T-cell tropic strains of HIV-1 fusion and entry of human white blood cells. CXCR4 is also required for the infection by dual-tropic strains of HIV-1 and mediates CD-4 independent infection by HIV-2. CXCR4 associates with the surface CD4-gp120 complex before HIV enters target cells. Antibodies to CXCR4 block HIV-1 and HIV-2 fusion and infection of human target cells. The amino-terminal domain and the second extracellular loop of CXCR4 serve as HIV s. Another G protein-coupled receptor CCR8 was also found to serve as a coreceptor for diverse T-cell tropic, dual-tropic and macrophage-tropic HIV-1 strains. CCR8 mediates CC chemokine I-309 induced monocyte chemoattraction and HIV-1 envelope fusion and virus infection, which can be prevented by the CCR8 ligand I-309. Other proteins that can function as viral cofactors include Bonzo, CX3CR1, DC-SIGN, and GPR15.
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