The Interferon Signaling Antagonist Function of Yellow Fever Virus NS5 Protein is Activated by Type I Interferon

Overview

Journal Cell Host Microbe

Publisher Cell Press

Specialties Infectious Diseases
Microbiology

Date 2014 Sep 12

PMID 25211074

Citations 106

Authors

Maudry Laurent-Rolle

Juliet Morrison

Ricardo Rajsbaum

Jesica M Levingston Macleod

Giuseppe Pisanelli

Alissa Pham

Juan Ayllon

Lisa Miorin

Carles Martinez

Benjamin R tenOever

Adolfo Garcia-Sastre

Affiliations

Soon will be listed here.

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.

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