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oai:riubu.ubu.es:10259/95292024-09-05T00:05:21Zcom_10259_4862com_10259_5086com_10259_2604col_10259_4863

00925njm 22002777a 4500 dc Laurent-Rolle, Maudry author Morrison, Juliet author Rajsbaum, Ricardo author Macleod, Jesica M. Levingston author Pisanelli, Giuseppe author Pham, Alissa author Ayllón Barasoain, Juan author Miorin, Lisa author Martínez Romero, Carles author tenOever, Benjamin R. author García Sastre, Adolfo author 2014-09 To successfully establish infection, flaviviruses have to overcome the antiviral state induced by type I interferon (IFN-I). The nonstructural NS5 proteins of several flaviviruses antagonize IFN-I signaling. Here we show that yellow fever virus (YFV) inhibits IFN-I signaling through a unique mechanism that involves binding of YFV NS5 to the IFN-activated transcription factor STAT2 only in cells that have been stimulated with IFN-I. This NS5-STAT2 interaction requires IFN-I-induced tyrosine phosphorylation of STAT1 and the K63-linked polyubiquitination at a lysine in the N-terminal region of YFV NS5. We identified TRIM23 as the E3 ligase that interacts with and polyubiquitinates YFV NS5 to promote its binding to STAT2 and trigger IFN-I signaling inhibition. Our results demonstrate the importance of YFV NS5 in overcoming the antiviral action of IFN-I and offer a unique example of a viral protein that is activated by the same host pathway that it inhibits. 1931-3128 http://hdl.handle.net/10259/9529 10.1016/j.chom.2014.07.015 The Interferon Signaling Antagonist Function of Yellow Fever Virus NS5 Protein Is Activated by Type I Interferon