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JVI Accepts, published online ahead of print on 3 September 2008
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J. Virol. doi:10.1128/JVI.01284-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Interferon-antagonistic ML protein of Thogoto virus targets general transcription factor IIB

Carola Vogt, Ellen Preuß, Daniel Mayer, Friedemann Weber, Martin Schwemmle, and Georg Kochs*

Department of Virology, University of Freiburg, Hermann-Herder-Strasse 11, 79104 Freiburg, Germany

* To whom correspondence should be addressed. Email: Georg.kochs{at}uniklinik-freiburg.de.


   Abstract

The ML protein of Thogoto virus (THOV), a tick-transmitted orthomyxovirus, is a splice variant of the viral matrix protein and antagonizes the induction of antiviral type I interferon (IFN). Here, we identified the general RNA polymerase II transcription factor IIB (TFIIB) as an ML-interacting protein. Overexpression of TFIIB neutralized the inhibitory effect of ML on IRF3-mediated promoter activation. Moreover, a recombinant virus expressing a mutant ML unable to bind TFIIB was severely impaired in its ability to suppress IFN induction. We conclude that TFIIB binding is required for the IFN-antagonistic effect exerted by ML. We further demonstrate that the ML-TFIIB interaction has surprisingly little impact on gene expression in general, while a strong negative effect is observed for IRF3- and NF{kappa}B-regulated promoters.







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