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<mods:namePart>Laurent-Rolle, Maudry</mods:namePart>
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<mods:namePart>Martínez Romero, Carles</mods:namePart>
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<mods:namePart>tenOever, Benjamin R.</mods:namePart>
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<mods:namePart>García Sastre, Adolfo</mods:namePart>
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<mods:dateIssued encoding="iso8601">2014-09</mods:dateIssued>
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<mods:identifier type="issn">1931-3128</mods:identifier>
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<mods:identifier type="doi">10.1016/j.chom.2014.07.015</mods:identifier>
<mods:abstract>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.</mods:abstract>
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<mods:title>The Interferon Signaling Antagonist Function of Yellow Fever Virus NS5 Protein Is Activated by Type I Interferon</mods:title>
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