Animal Models Recapitulate Aspects of HIV/CNS Disease

Neurobehavioral and pathological data indicate that the central nervous system (CNS) becomes infected with HIV-1 soon after the virus enters the body. However, neuropathogenesis of HIV-1 infection is difficult to investigate because the brain parenchyma is not accessible to sampling during the course of AIDS. The second compartment of the CNS, cerebrospinal fluid (CSF), is accessible to sampling but how changes in the CSF relate to the changes in the parenchyma is poorly understood. Thus, knowledge of the neuropathogenesis of HIV-1 infection predominantly stems from either postmortem or in vitro studies. This raises the need for animal models of HIV infection of the CNS. Such models have been developed and are briefly reviewed here. The models faithfully recapitulate some aspects of the HIV/CNS disease. Appropriate neuropathological changes and neurobehavioral dysfunction (e.g., cognitive and motor deficits) occur in SIV-infected macaques. Central sensory electrophysiological changes and sleep disturbances occur in FIV-infected cats. Infection of the brain and behavioral changes comparable to some of the changes seen in humans occur in mice infected with a mixture of murine leukemia viruses. Genetically immunodeficient mice (e.g., SCID) accept HIV-infected human organs and or cell grafts. Evidence summarized here indicates that these HuSCID animals undergo neuropathological changes similar to those observed in brains of individuals who died with AIDS. Thus, presently available animal models provide an opportunity to investigate HIV/CNS disease, and to develop and test therapeutic interventions to prevent or cure the disease.