In vivo transcriptional regulation of the human immunodeficiency virus in the central nervous system in transgenic mice

Abstract

Human immunodeficiency virus type 1 (HIV-1) causes infections of the central nervous system (CNS) and has been implicated as the causative agent of AIDS-associated encephalopathy and the AIDS dementia complex. The development of in vivo models of HIV-1-mediated gene expression has shown that the HIV long terminal repeat (LTR) from the viral isolate HIV(JR-CSF) specifically supports gene expression in adult and developing CNS. To determine the molecular basis for HIV-1 developmental CNS gene expression, in vivo footprinting analysis by the ligation-mediated PCR technique was performed on CNS tissue from the brain stem of a transgenic mouse. The association of cellular proteins in the CNS with sequences in the LTR was found over sequences that defined the TATA region, the Sp-1 and NF-kappaB sites, and two upstream regions (-111 to -150 and -260 to -300). A purine-rich sequence at positions -256 to -296 of the HIV(JR-CSF) LTR but not of the HIV(IIIB) LTR specifically bound protein in nuclear extracts of newborn brain tested in electrophoretic mobility shift assays. No specific protein binding was observed to this region in liver or HeLa cell nuclear extracts. This suggests the presence of a newly identified transcription factor involved in regulation of HIV-1 gene expression in the CNS.