{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Laurent-Rolle M"],"funding":["NIAID NIH HHS","PHS HHS"],"pagination":["314-327"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4176702"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["16(3)"],"pubmed_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."],"journal":["Cell host & microbe"],"pubmed_title":["The interferon signaling antagonist function of yellow fever virus NS5 protein is activated by type I interferon."],"pmcid":["PMC4176702"],"funding_grant_id":["U54AI057158","U54 AI057158","FAI077333A"],"pubmed_authors":["Morrison J","Pisanelli G","tenOever BR","Macleod JML","Garcia-Sastre A","Rajsbaum R","Laurent-Rolle M","Miorin L","Martinez C","Ayllon J","Pham A"],"additional_accession":[]},"is_claimable":false,"name":"The interferon signaling antagonist function of yellow fever virus NS5 protein is activated by type I interferon.","description":"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.","dates":{"release":"2014-01-01T00:00:00Z","publication":"2014 Sep","modification":"2024-11-19T19:34:01.877Z","creation":"2019-03-27T01:36:33Z"},"accession":"S-EPMC4176702","cross_references":{"pubmed":["25211074"],"doi":["10.1016/j.chom.2014.07.015"]}}