Chemokine receptors and mechanisms of cell death in HIV neuropathogenesis

Several chemokine receptors are used as coreceptors for HIV-1 entry in the central nervous system (CNS). CCR5 is the major coreceptor together with CD 4 for HIV-1 infection of microglia, the major target cells for HIV-1 infect ion in the CNS. CXCR4 and CCR3 are also expressed on microglia and can medi ate infection by certain HIV-1 isolates but at lower efficiency than CCR5, Additional chemokine coreceptors are expressed in the brain, but their role in HIV-1 neuropathogenesis has not been defined. The expression of CXCR4, and possibly other chemokine receptors, on subpopulations of neurons and gl ial cells may render neurons vulnerable to mechanisms of CNS injury induced by the HIV-1 gp120 Env protein. HIV-1 viruses which use CXCR4 and emerge d uring the late stages of HIV-1 infection may impact disease progression in the CNS by inducing apoptosis of neurons and other cell types. The neurodeg enerative mechanisms may involve infection of microglia by certain CXCR4 tr opic viruses in addition to cellular dysfunction and apoptosis induced by H IV-1 gp120 binding to CXCR4. Understanding the role of CXCR4 and other chem okine receptors in HIV-1 neuropathogenesis will help to advance the develop ment of new therapeutic strategies for the prevention and treatment of neur ologic disorders associated with HIV-1 infection.