CCR3 and CCR5 Are Co-Receptors for HIV-1 Infection of Microglia

Nature. 1997 Feb 13;385(6617):645-9. doi: 10.1038/385645a0.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Alzheimer Disease / metabolism
  • Antibodies, Monoclonal / immunology
  • Brain / cytology
  • CD4 Antigens / metabolism
  • Cells, Cultured
  • Chemokine CCL11
  • Chemokines / pharmacology
  • Chemokines, CC*
  • Cytokines / pharmacology
  • Gene Products, env / metabolism
  • HIV-1 / metabolism*
  • Humans
  • Lectins / metabolism
  • Ligands
  • Luciferases / genetics
  • Microglia / virology*
  • Plant Lectins*
  • Receptors, CCR3
  • Receptors, CCR5
  • Receptors, Chemokine*
  • Receptors, Cytokine / drug effects
  • Receptors, Cytokine / metabolism*
  • Receptors, HIV / drug effects
  • Receptors, HIV / metabolism*

Substances

  • Antibodies, Monoclonal
  • CCL11 protein, human
  • CCR3 protein, human
  • CD4 Antigens
  • Chemokine CCL11
  • Chemokines
  • Chemokines, CC
  • Cytokines
  • Gene Products, env
  • Lectins
  • Ligands
  • Plant Lectins
  • Receptors, CCR3
  • Receptors, CCR5
  • Receptors, Chemokine
  • Receptors, Cytokine
  • Receptors, HIV
  • Ricinus communis agglutinin-1
  • Luciferases