Examination of TAR-independent Trans activation by human immunodeficiency virus type 1 Tat in human glial cells.

Abstract

Astrocytic glial cells derived from central nervous system (CNS) can support human immunodeficiency virus type 1 (HIV-1) replication in cell culture, may be infected in tissue culture, and are thought to be a large 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 and, in certain circumstances, an HIV-1 long terminal repeat (LTR) that lacks the TAR element. Therefore, we attempted to investigate Tat trans activation of HIV-1 LTR in the astrocytic glial cells. Using transfection 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 element. 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 cells. However, in astrocytic glial cells, the trans activation of env expression from the LTR-lacking TAR element was mediated by the first exon peptide of Tat as well as the full-length Tat peptide through a post-transcriptional mechanism rather than a transcriptional one. This result suggests that cell type-specific factor(s) is involved in the TAR-independent Tat responsiveness.