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 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.
Kim
Y S
YS
Institute of Cancer Research, College of Medicine, Yonsei University, Seoul, Korea.
Panganiban
A T
AT
D001254:Astrocytoma / Q000378:metabolism; D002459:Cell Fusion / Q000502:physiology; D015696:Gene Products, tat / Q000096:biosynthesis / Q000235:genetics*; D015752:Genes, env / Q000502:physiology; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism*; D010957:Plasmids; D011233:Precipitin Tests; D015533:Transcriptional Activation / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D014764:Viral Proteins / Q000096:biosynthesis; D014779:Virus Replication / Q000502:physiology; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D014764:Viral Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; D008156:Luciferases