RT info:eu-repo/semantics/article
T1 The Interferon Signaling Antagonist Function of Yellow Fever Virus NS5 Protein Is Activated by Type I Interferon
A1 Laurent-Rolle, Maudry
A1 Morrison, Juliet
A1 Rajsbaum, Ricardo
A1 Macleod, Jesica M. Levingston
A1 Pisanelli, Giuseppe
A1 Pham, Alissa
A1 Ayllón Barasoain, Juan
A1 Miorin, Lisa
A1 Martínez Romero, Carles
A1 tenOever, Benjamin R.
A1 García Sastre, Adolfo
K1 Medicina
K1 Medicine
K1 Salud
K1 Health
K1 Microbiología
K1 Microbiology
K1 Enfermedades infecciosas
K1 Communicable diseases
AB 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.
PB Cell Press
SN 1931-3128
YR 2014
FD 2014-09
LK http://hdl.handle.net/10259/9529
UL http://hdl.handle.net/10259/9529
LA eng
NO 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.
DS Repositorio Institucional de la Universidad de Burgos
RD 23-nov-2024