2026-05-05T00:20:40Zhttps://riubu.ubu.es/oai/request

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

Laurent-Rolle, Maudry Morrison, Juliet Rajsbaum, Ricardo Macleod, Jesica M. Levingston Pisanelli, Giuseppe Pham, Alissa Ayllón Barasoain, Juan Miorin, Lisa Martínez Romero, Carles tenOever, Benjamin R. García Sastre, Adolfo 2024-09-04T12:21:05Z 2024-09-04T12:21:05Z 2014-09 1931-3128 http://hdl.handle.net/10259/9529 10.1016/j.chom.2014.07.015 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. 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. application/pdf eng Cell Press Cell Host & Microbe. 2014, V. 16, n. 3, p. 314-327 https://doi.org/10.1016/j.chom.2014.07.015 info:eu-repo/grantAgreement/NIAID//U54AI057158/US/ info:eu-repo/grantAgreement/NIH//FAI077333A/US/ Attribution-NonCommercial-NoDerivatives 4.0 Internacional http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess Medicina Salud Microbiología Enfermedades infecciosas Medicine Health Microbiology Communicable diseases The Interferon Signaling Antagonist Function of Yellow Fever Virus NS5 Protein Is Activated by Type I Interferon info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion Cell Host & Microbe 16 3 314 327