2026-05-04T22:20:01Zhttps://riubu.ubu.es/oai/request

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

The Interferon Signaling Antagonist Function of Yellow Fever Virus NS5 Protein Is Activated by Type I Interferon 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 Medicina Salud Microbiología Enfermedades infecciosas Medicine Health Microbiology Communicable diseases 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. 2024-09-04T12:21:05Z 2024-09-04T12:21:05Z 2014-09 info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion 1931-3128 http://hdl.handle.net/10259/9529 10.1016/j.chom.2014.07.015 eng 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 application/pdf Cell Press https://riubu.ubu.es/bitstream/10259/9529/4/Laurent-chm_2014.pdf.jpg Hispana TEXT http://creativecommons.org/licenses/by-nc-nd/4.0/ RIUBU. Repositorio Institucional de la Universidad de Burgos http://hdl.handle.net/10259/9529