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<field name="value">Laurent-Rolle, Maudry</field>
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<field name="value">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.</field>
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<field name="value">These studies were partly supported by NIAID grant U54AI057158 (to A.G.-S.) and by NIH fellowship FAI077333A (to M.L.-R.). We thank Richard Cadagan and Osman Lizardo for technical assistance, and Dr. Adriana Forero for editorial help. Confocal laser scanning microscopy was performed at ISMMS-Microscopy Shared Resource facility.</field>
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<field name="value">Cell Host &amp; Microbe. 2014, V. 16, n. 3, p. 314-327</field>
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