Chemokine receptors and virus entry in the central nervous system

Several members of the chemokine receptor family are used as coreceptors together with CD4 for HIV and SIV entry in the central nervous system (CNS). CCR5 is the major coreceptor for HIV-1 infection of macrophages and microglia, the major target cells for HIV-1 infection in the CNS. CXCR4 and CCR3 are also expressed on microglia and can mediate infection by certain HIV-1 isolates but at lower efficiency than CCR5. Additional chemokine receptors that can function as HIV-1 and SIV coreceptors for a subset of viruses are expressed in the brain (i.e. Apj, CX3CR1, STRL33/BONZO, and gpr1), but their role in CNS infection has not been defined. The expression of CXCR4, and possibly other chemokine receptors, on subpopulations of neurons and glial cells may contribute to mechanisms of CNS injury that are independent of viral infection. Understanding the role of chemokine receptors and their chemokine ligands in HIV-1 and SIV infection of the CNS will elucidate mechanisms of viral tropism and pathogenesis and advance the development of new therapeutic strategies.