Effect of Alcohol on SHIV Neuroinvasion

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DESCRIPTION (provided by applicant): Approximately 20% of humans infected with human immunodeficiency virus type 1 (HIV-1) develop a neurological disease known as HIV-associated cognitive/motor complex or AIDS dementia complex. It is known that chronic use of ethanol can lead to an immunocompromised state that results in increased susceptibility to bacterial and viral pathogens. A significant number of HIV-1 positive individuals drink moderate to excessive amounts of alcohol. Detailed studies directly assessing the role of alcohol on HIV-1 neuroinvasion and neuropathogenesis have not been performed in a relevant animal model system. The investigator's laboratory has derived a variant of simian-human immunodeficiency virus (SHIV500LNV) that following inoculation into pig-tailed macaques, results in high virus burdens, depletion of the CD4+ subset of T cells, and a neuropathology (perivascular cuffing, microglial nodules) in 50% of the macaques that is similar to that seen in HIV-1 infected humans. In the proposed studies, the investigators propose to use the neuropathogenic SHIV/macaque model to determine if alcohol can directly affect the early events of neuroinvasion as well as the incidence of SHIV-induce encephalitis. Sixteen macaques will be placed on a self-administered ethanol diet to model moderate drinking and sixteen macaques on lacking ethanol for 9 months. At this point, sixteen macaques (eight on the ethanol diet and eight on the ethanol free diet) will be inoculated with SHIV500LNV, maintained on their ethanol diet and sacrificed at 2 weeks to determine if self-administered ethanol will result in increased neuroinvasion during the primary phase of infection, which is a period of unrestricted virus replication and when the host has not yet developed an effective immune response against the virus. In the second group of sixteen macaques (again eight on the ethanol diet and eight on the ethanol-free diet), the virus will be inoculated and macaques followed until moribund to determine if an ethanol diet will result in an increased incidence of neurological disease. The results of these studies should provide direct evidence on the effect of ethanol on primate lentivirus neuroinvasion and neuropathogenesis.