CCR3 and CCR5 are co-receptors for HIV-1 infection of microglia

• Published in: Nature (London) Vol. 385; no. 6617; pp. 645 - 649
• Main Authors: He, Jianglin, Chen, Youzhi, Farzan, Michael, Choe, Hyeryun, Ohagen, Asa, Gartner, Suzanne, Busciglio, Jorge, Yang, Xiaoyu, Hofmann, Wolfgang, Newman, Walter, Mackay, Charles R, Sodroski, Joseph, Gabuzda, Dana
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 13.02.1997; Nature Publishing Group
• Subjects: Adult; AIDS/HIV; Alzheimer Disease - metabolism; Antibodies, Monoclonal - immunology; Biological and medical sciences; Brain; Brain - cytology; CD4 Antigens - metabolism; Cells, Cultured; Cellular biology; Central nervous system; Chemokine CCL11; Chemokines - pharmacology; Chemokines, CC; Cytokines - pharmacology; Dementia disorders; Fundamental and applied biological sciences. Psychology; Gene Products, env - metabolism; HIV; HIV-1 - metabolism; Human immunodeficiency virus; human immunodeficiency virus 1; Humans; Lectins - metabolism; Ligands; Luciferases - genetics; Microbiology; Microglia - virology; Nervous system; Plant Lectins; Receptors, CCR3; Receptors, CCR5; Receptors, Chemokine; Receptors, Cytokine - drug effects; Receptors, Cytokine - metabolism; Receptors, HIV - drug effects; Receptors, HIV - metabolism; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; Virology; Human; HIV-1 virus; Neuroglia; Cytokine; Central nervous system; Retroviridae; Host virus relation; Microglia; Virus; Chemokine; Cell line; Lentivirinae; Human immunodeficiency virus; Virus penetration; Macrophage; Biological receptor
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/385645a0

Several members of the chemokine receptor family are used together with CD4 for HIV-1 entry into target cells. T cell line-tropic (T-tropic) HIV-1 viruses use the chemokine receptor CXCR4 as a co-receptor, whereas macrophage-tropic (M-tropic) primary viruses use CCR5 (refs 2-6). Individuals with defective CCR5 alleles exhibit resistance to HIV-1 infection, suggesting that CCR5 has an important role in vivo in HIV-1 replication. A subset of primary viruses can use CCR3 as well as CCR5 as a co-receptor, but the in vivo contribution of CCR3 to HIV-1 infection and pathogenesis is unknown. HIV-1 infects the central nervous system (CNS) and causes the dementia associated with AIDS. Here we report that the major target cells for HIV-1 infection in the CNS, the microglia, express both CCR3 and CCR5. The CCR3 ligand, eotaxin, and an anti-CCR3 antibody inhibited HIV-1 infection of microglia, as did MIP-1beta, which is a CCR5 ligand. Our results suggest that both CCR3 and CCR5 promote efficient infection of the CNS by HIV-1.