GENETICS OF NEUROPATHOGENIC SIV INFECTION

Harvard Medical School, Boston MA

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. HIV-associated dementia is a progressive neurological condition that affects a significant proportion of HIV-infected people, and occurs as a result of viral replication in the brain. HIV enters the brain (neuroinvasion) by the transmigration of infected blood monocytes across the blood-brain barrier during normal immune surveillance of the central nervous system. Although HIV-infected monocytes can probably be found in the circulation of all seropositive individuals, not all HIV-positive people develop HIV encephalitis (HIVE) or HIV-associated dementia. This suggests that viral determinants or host immunity play an important role in determining whether HIV infection becomes established in the brain. We have developed a nonhuman primate model of HIVE that uses an isolate (SIVsmmFGb) of simian immunodeficiency virus (SIV) that is highly neuropathogenic in pigtailed macaque monkeys. Dr. Novembre is using this model at the Yerkes Center to investigate the influence of viral determinants on neuroinvasion and the pathogenesis of SIVE, while we are using this model to investigate the impact of the innate and adaptive immune responses on the earliest stages of SIV encephalitis (SIVE).