Human T-cell leukemia virus type 1 Tax modulates interferon-alpha signal transduction through competitive usage of the coactivator CBP/p300.

We describe here Tax protein of human T-cell leukemia virus type 1 (HTLV-1) as an interferon (IFN)-alpha antagonist counteracting the transactivation function of IFN-stimulated gene factor 3 (ISGF3). Co-expression of Tax, but not the Tax mutant unable to bind to CBP, significantly inhibited the reporter gene expression directed by IFN-stimulated ...
regulatory elements, despite that the formation of DNA-binding ISGF3 complex was unaffected. Gene activation induced by STAT2 transcription domain was also inhibited by expression of Tax. Furthermore, Tax-mediated transcriptional inhibition was reversed by overexpression of p300. These observations indicate that Tax interferes with IFN-alpha-induced JAK-STAT pathway by competition with STAT2 for CBP/p300 binding. Consistently, GST pull-down assay showed that Tax dose-dependently inhibited binding of STAT2 to p300. This study suggests that Tax may prevent IFN-alpha from exerting its antiviral, antiproliferative and proapoptotic effects, thereby contributing to persistent viral infection and HTLV-1-associated oncogenesis.
Mesh Terms:
Base Sequence, Binding, Competitive, CREB-Binding Protein, Cell Line, DNA Primers, Down-Regulation, Gene Products, tax, Genes, pX, HTLV-I Infections, HeLa Cells, Human T-lymphotropic virus 1, Humans, Interferon-Stimulated Gene Factor 3, Interferon-alpha, Jurkat Cells, Mutation, Recombinant Proteins, STAT2 Transcription Factor, Signal Transduction, Transcriptional Activation
Virology
Date: Sep. 30, 2008
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