Chemokine receptors in HIV-1 infection of the central nervous system

Several members of the chemokine receptor are used as coreceptors for HIV-1 infection in the central nervous system (CNS). CCR5 and CCR3 are coreceptors together with CD4 for HIV-1 infection of microglia, the major target for HIV-1 infection in the CNS. Microglia express CXCR4, but their infection by HIV-1 viruses that use only CXCR4 as a coreceptor is relatively inefficient. CXCR4 is also expressed in subpopulations of neurons that are resistant to HIV-1 infection. Additional orphan chemokine receptors that can mediate HIV-1 or SIV entry are expressed in the brain or neurally-derived cell lines, but their role in CNS infection has not been defined. The pattern of chemokine receptor expression in the brain is likely to determine the tropism of HIV-1 for particular CNS target cells and to impact inflammatory and degenerative mechanisms associated with CNS infection.