EXAMINATION OF TAR-INDEPENDENT TRANS ACTIVATION BY HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 TAT IN HUMAN GLIAL-CELLS

Astrocytic glial cells derived from central nervous system (CNS) can s upport human inmunodeficiency virus type 1 (HIV-1) replication in cell culture, may be infected in tissue culture, and are thought to be a l arge HIV-1 reservoir in vivo, The Tat protein of HIV-1 interacts with a cis-acting target sequence referred to as TAR, However, Tat can also stimulate gene expression directed from some heterologous promoters a nd, in certain circumstances, an HIV-1 long terminal repeat (LTR) that lacks the TAR element, Therefore, we attempted to investigate Tat tra ns activation of HIV-I LTR in the astrocytic glial cells, Using transf ection of LTR-reporter gene constructs and HIV-1 proviral constructs, we demonstrate TAR-dependent replication in astrocytic cells, We also examined the expression of HIV-1 env gene from an LTR that lacks TAR e lement, In a previous study (Kim and Panganiban: J Virol 67:3739-3747, 1993), we observed that env expression is trans activated only by the full-length Tat protein through a TAR-independent manner in HeLa cell s, However, in astrocytic glial cells, the trans activation of env exp ression from the LTR-lacking TAR element was mediated by the first exo n peptide of Tat as well as the full-length Tat peptide through a post -transcriptional mechanism rather than a transcriptional one. This res ult suggests that cell type-specific factor(s) is involved in the TAR- independent Tat responsiveness. (C) 1996 Wiley-Liss, Inc.