Repression of tumor necrosis factor-β 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-β (TNF-β) promoter-directed gene expression in lymphocytic and monocytic cell lines and further demonstrate that a ‘TAR-like structureʹ downstream of the TNF-β promoter is essential for Tat activity. The ability of Tat to activate TNF-β 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-β 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-β repression. Tat repression of TNF-β, 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.