IN-VIVO TRANSCRIPTIONAL REGULATION OF THE HUMAN-IMMUNODEFICIENCY-VIRUS IN THE CENTRAL-NERVOUS-SYSTEM IN TRANSGENIC MICE

Human immunodeficiency virus type 1 (HIV-1) causes infections of the c entral nervous system (CNS) and has been implicated as the causative a gent of AIDS-associated encephalopathy and the AIDS dementia complex. The development of in vivo models of HIV-1-mediated gene expression ha s shown that the HIV long terminal repeat (LTR) from the viral isolate HIVJR-CSF specifically supports gene expression in adult and developi ng CNS. To determine the molecular basis for HIV-1 developmental CNS g ene expression, in vivo footprinting analysis by the ligation-mediated PCR technique was performed on CNS tissue from the brain stem of a tr ansgenic mouse. The association of cellular proteins in the CNS with s equences in the LTR was found over sequences that defined the TATA reg ion, the Sp-1 and NF-kappa B sites, and two upstream regions (-111 to -150 and -260 to -300). A purine-rich sequence at positions -256 to -2 96 of the HIVJR-CSF LTR but not of the HIVIIIB LTR specifically bound protein in nuclear extracts of newborn brain tested in electrophoretic mobilia shift assays. No specific protein binding was observed to thi s region in liver or HeLa cell nuclear extracts. This suggests the pre sence of a newly identified transcription factor involved in regulatio n of HIV-1 gene expression in the CNS.