Elsevier

Virology

Volume 379, Issue 2, 30 September 2008, Pages 306-313
Virology

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

https://doi.org/10.1016/j.virol.2008.06.035Get rights and content
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Abstract

We describe here Tax protein of human T-cell leukemia virus type 1 (HTLV-1) as an interferon (IFN)-α 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-α-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-α from exerting its antiviral, antiproliferative and proapoptotic effects, thereby contributing to persistent viral infection and HTLV-1-associated oncogenesis.

Keywords

HTLV-1
Tax
IFN-α signaling
CBP/p300 coactivator

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