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Suppression of type I interferon production by human T-cell leukemia virus type 1 oncoprotein Tax

Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia (ATL) and tropical spastic paraparesis. Type I interferons are key effectors of innate antiviral response and have been tested as anti-HTLV-1 and anti-ATL agents. HTLV-1 oncoprotein Tax is known to suppress innate interferon response by activating SOCS1, an inhibitor of interferon signaling that activates the expression of interferon-stimulated genes. Whether Tax might also suppress interferon production remains to be determined. Here we report on the suppression of type I interferon production by HTLV-1 Tax through interaction with and inhibition of TBK1 kinase. HTLV-1-transformed ATL cells were found to be unable to boost the production of type I interferons in response to Sendai virus infection. This inability was attributed to Tax. Expression of Tax alone sufficiently repressed the induction of interferon production by RIG-I + PACT, TBK1 and IRF3, but not by IRF3-5D, a dominant active phosphomimetic mutant. This suggests that Tax might act at a point prior to IRF3 phosphorylation. Reciprocal co-immunoprecipitation and immunoblotting experiments confirmed the association of Tax with TBK1 kinase that phosphorylates IRF3. In vitro kinase assay indicated an inhibitory effect of Tax on TBK1-mediated phosphorylation of IRF3. Taken together, our findings suggested a new mechanism by HTLV-1 oncoprotein Tax circumvents the production of type I interferons in infected cells. (Supported by HKU7661/08M, HKU7674/12M, HKU1/CRF/11G and SKY-MRF-2011).

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Correspondence to Dong-Yan Jin.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

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Jin, DY., Kok, KH., Tang, HM.V. et al. Suppression of type I interferon production by human T-cell leukemia virus type 1 oncoprotein Tax. Retrovirology 11 (Suppl 1), P77 (2014).

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