CCR3 and CCR5 are co-receptors for HIV-1 infection of microglia.
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.
He
J
J
Division of Human Retrovirology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Chen
Y
Y
Farzan
M
M
Choe
H
H
Ohagen
A
A
Gartner
S
S
Busciglio
J
J
Yang
X
X
Hofmann
W
W
Newman
W
W
Mackay
C R
CR
Sodroski
J
J
Gabuzda
D
D
D000328:Adult; D000544:Alzheimer Disease / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000276:immunology; D001921:Brain / Q000166:cytology; D015704:CD4 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D054413:Chemokine CCL11; D018925:Chemokines / Q000494:pharmacology; D019742:Chemokines, CC; D016207:Cytokines / Q000494:pharmacology; D015686:Gene Products, env / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D037102:Lectins / Q000378:metabolism; D008024:Ligands; D008156:Luciferases / Q000235:genetics; D017628:Microglia / Q000821:virology*; D037121:Plant Lectins; D054397:Receptors, CCR3; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000187:drug effects / Q000378:metabolism*; D015728:Receptors, HIV / Q000187:drug effects / Q000378:metabolism*
D000911:Antibodies, Monoclonal; C515456:CCL11 protein, human; C515350:CCR3 protein, human; D015704:CD4 Antigens; D054413:Chemokine CCL11; D018925:Chemokines; D019742:Chemokines, CC; D016207:Cytokines; D015686:Gene Products, env; D037102:Lectins; D008024:Ligands; D037121:Plant Lectins; D054397:Receptors, CCR3; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D015728:Receptors, HIV; C017707:Ricinus communis agglutinin-1; D008156:Luciferases