Repression of tumor necrosis factor-beta expression by the human immunodeficiency virus type-1 tat protein in central nervous system-derived glial cells.
HIV-1 Tat is a potent transactivator that stimulates expression from the HIV-1 LTR, from certain cellular gene promoters and from several heterologous viral promoters. Previous reports show that HIV-1 Tat transactivates tumor necrosis factor-beta (TNF-beta) promoter-directed gene expression in lymphocytic and monocytic cell lines and further demonstrate that a 'TAR-like structure' downstream of the TNF-beta promoter is essential for Tat activity. The ability of Tat to activate TNF-beta may have profound effects as TNF has been shown to be a potent activator of HIV-1 gene expression and an important immunomodulatory and growth regulatory factor. The studies presented herein demonstrate a novel finding where HIV-1 Tat specifically represses (> 10-fold) TNF-beta promoter-directed gene expression in central nervous system-derived glial cells. Amino acid residues 2 to 36 of HIV-1 Tat are required for TNF-beta repression. Tat repression of TNF-beta, a factor which upregulates HIV-1 gene expression, suggests a novel mechanism whereby HIV-1 is able to establish latent infection of glial cells that present no detectable virions and/or viral antigens.
Yang
L
L
School of Biology, Georgia Institute of Technology, Atlanta 30332, USA.
Morris
G F
GF
Wang
Z
Z
Bohan Morris
C
C
D001253:Astrocytes / Q000187:drug effects / Q000821:virology; D002490:Central Nervous System / Q000166:cytology / Q000187:drug effects / Q000821:virology*; D005786:Gene Expression Regulation / Q000187:drug effects; D015696:Gene Products, tat / Q000235:genetics / Q000502:physiology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008233:Lymphotoxin-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D010446:Peptide Fragments / Q000737:chemistry / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000187:drug effects; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D008233:Lymphotoxin-alpha; D010446:Peptide Fragments; D054322:tat Gene Products, Human Immunodeficiency Virus