IRE1α Promotes Zika Virus Infection via XBP1.

Viruses
Elena P KolpikovaSusan L Fink

Abstract

Zika virus (ZIKV) is an emergent member of the Flaviviridae family which causes severe congenital defects and other major sequelae, but the cellular processes that support ZIKV replication are incompletely understood. Related flaviviruses use the endoplasmic reticulum (ER) as a membranous platform for viral replication and induce ER stress during infection. Our data suggest that ZIKV activates IRE1α, a component of the cellular response to ER stress. IRE1α is an ER-resident transmembrane protein that possesses a cytosolic RNase domain. Upon activation, IRE1α initiates nonconventional cytoplasmic splicing of XBP1 mRNA. Spliced XBP1 encodes a transcription factor, which upregulates ER-related targets. We find that ZIKV infection induces XBP1 mRNA splicing and induction of XBP1 target genes. Small molecule inhibitors of IRE1α, including those specific for the nuclease function, prevent ZIKV-induced cytotoxicity, as does genetic disruption of IRE1α. Optimal ZIKV RNA replication requires both IRE1α and XBP1. Spliced XBP1 has been described to cause ER expansion and remodeling and we find that ER redistribution during ZIKV infection requires IRE1α nuclease activity. Finally, we demonstrate that inducible genetic disruption of IRE1α a...Continue Reading

References

Oct 16, 2003·Molecular and Cellular Biology·Ann-Hwee LeeLaurie H Glimcher
Feb 13, 2004·The Journal of Biological Chemistry·Keith D TardifAleem Siddiqui
Dec 20, 2005·The EMBO Journal·Ann-Hwee LeeLaurie H Glimcher
Aug 6, 2008·Emerging Infectious Diseases·Robert S LanciottiMark R Duffy
Aug 9, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Donna SirJing-Hsiung James Ou
Aug 5, 2009·The Journal of Cell Biology·Julie HollienJonathan S Weissman
Aug 22, 2009·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Michael S Diamond
Mar 10, 2011·The Journal of Biological Chemistry·José Peña, Eva Harris
Feb 9, 2012·Proceedings of the National Academy of Sciences of the United States of America·Benedict C S CrossHeather P Harding
Aug 31, 2013·Nature Reviews. Drug Discovery·Claudio HetzHeather P Harding
Mar 19, 2014·The Journal of Cell Biology·Annamaria RuggianoPedro Carvalho
May 6, 2014·Frontiers in Genetics·Dina S Coelho, Pedro M Domingos
May 9, 2014·The Journal of Clinical Investigation·Chih-Hang Anthony TangChih-Chi Andrew Hu
Jun 12, 2014·Frontiers in Microbiology·Ana-Belén BlázquezMiguel A Martín-Acebes
Aug 30, 2014·Critical Reviews in Microbiology·Shanshan LiXilan Yu
Dec 15, 2015·Developmental Cell·Sophie LaguesseLaurent Nguyen
Mar 10, 2016·Annual Review of Virology·David Paul, Ralf Bartenschlager
Apr 14, 2016·Cell Host & Microbe·Helen M LazearMichael S Diamond
Jun 11, 2016·The Lancet Infectious Diseases·Nitwara Wikan, Duncan R Smith
Sep 11, 2016·Cell Reports·Jonathan J MinerRajendra S Apte
Nov 1, 2016·Nature·Jennifer GoveroMichael S Diamond
Jan 14, 2017·Proceedings of the National Academy of Sciences of the United States of America·Wenhua GaoWilliam G Kaelin
Feb 1, 2017·Proceedings of the National Academy of Sciences of the United States of America·Ozlem TufanliEbru Erbay
Mar 2, 2017·Cell Reports·Mirko CorteseRalf Bartenschlager
Mar 7, 2017·Science Advances·Ryuta UrakiErol Fikrig

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Datasets Mentioned

BETA
GTX133311
PA116927

Methods Mentioned

BETA
electrophoresis
Infrared Imaging
ESR
ubiquitination

Software Mentioned

Image J
Image Studio Lite

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