Apoptosis and HIV neuropathogenesis

A consequence of HIV infection may be neurological dysfunction secondary to the presence of virus in the central nervous system (CNS). The CNS tropism of HIV and the mechanisms that govern its dissemination are not well defined. One view is that HIV enters the brain through the diapedesis of infected monocytes from blood into the perivascular space. HIV may then spread to susceptible cells throughout parenchyma. An alternate hypothesis is presented, which suggests that T lymphocyte apoptosis may also participate in HIV entry and dissemination in the brain. This is based on the following observations: 1) T lymphocyte apoptosis may be a CNS-specific mechanisms to control inflammation, 2) the most common circulating reservoir of HIV is the T lymphocyte, 3) uninfected macrophages recruited to phagocytize HIV infected apoptotic T lymphocytes in vitro can become productively infected, and 4) the predominant form of HIV in the CNS is unintegrated. Aberrantly high levels of apoptosis in HIV infected lymphocytes within the CNS and subsequent recruitment and infection of macrophages and microglia may be a novel component of HIV neuropathogenesis.