HIV, the causative agent of AIDS and presumptive agent for AIDS associated dementia ad subacute encephalitis, is a non-oncogenic retrovirus with an unusually long incubation period prior to the clinical manifestation of disease. HIV is morphologically, genetically and biologically related to the other lentiviruses. These viruses have in common a long latent period and multi-organ disease with progressive neurological involvement. Macrophages have been identified as the major HIV infected cell in the CNS. HIV infection of macrophages is not cytopathologic either in vivo or in vitro and these cells may serve as a reservoir for HIV infection.
An aim of this proposal is to examine the role of the HIV LTR in activation of viral gene expression in the macrophage and the role of this cell in HIV infection of the CNS and PNS. In addition, the role of the HIV TAT in activating viral gene expression and effecting normal cellular functions will be studied. The HIV LTR will be linked to a reporter gene (the bacterial enzyme chloramphenicol acetyltransferase, CAT) and this construct will be used to produce transgenic mice. The expression of CAT activity will be examined in all tissues of the transgenic mouse to determine the role of the HIV LTR in Tissue tropism. It will be determined if secondary factors (viral infections or insults to the CNS or PNS), which cause activation of macrophages, affect homing of macrophages to the CNS or PNS. In addition, the HIV-TAT gene will be used to construct transgenic mice to examine the role of this gene in viral activation and cellular pathology in vivo. These studies should reveal the contribution of single viral genetic elements - the HIV LTR and the TAT gene to CNS and PNS pathogenesis.
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