2'-O methylation of the viral mRNA cap evades host restriction by IFIT family members

Nature
Stephane DaffisMichael S Diamond

Abstract

Cellular messenger RNA (mRNA) of higher eukaryotes and many viral RNAs are methylated at the N-7 and 2'-O positions of the 5' guanosine cap by specific nuclear and cytoplasmic methyltransferases (MTases), respectively. Whereas N-7 methylation is essential for RNA translation and stability, the function of 2'-O methylation has remained uncertain since its discovery 35 years ago. Here we show that a West Nile virus (WNV) mutant (E218A) that lacks 2'-O MTase activity was attenuated in wild-type primary cells and mice but was pathogenic in the absence of type I interferon (IFN) signalling. 2'-O methylation of viral RNA did not affect IFN induction in WNV-infected fibroblasts but instead modulated the antiviral effects of IFN-induced proteins with tetratricopeptide repeats (IFIT), which are interferon-stimulated genes (ISGs) implicated in regulation of protein translation. Poxvirus and coronavirus mutants that lacked 2'-O MTase activity similarly showed enhanced sensitivity to the antiviral actions of IFN and, specifically, IFIT proteins. Our results demonstrate that the 2'-O methylation of the 5' cap of viral RNA functions to subvert innate host antiviral responses through escape of IFIT-mediated suppression, and suggest an evoluti...Continue Reading

References

Jan 1, 1975·Proceedings of the National Academy of Sciences of the United States of America·C M Wei, B Moss
Dec 23, 1998·Proceedings of the National Academy of Sciences of the United States of America·S D DerR H Silverman
Oct 29, 2000·Advances in Virus Research·Y Furuichi, A J Shatkin
Oct 7, 2004·Pharmacology & Therapeutics·Saumendra N Sarkar, Ganes C Sen
Nov 25, 2004·The Journal of Biological Chemistry·Daniel J HuiGanes C Sen
Apr 16, 2005·The Journal of General Virology·Pierre Fechter, George G Brownlee
Feb 3, 2007·Journal of Virology·Yangsheng ZhouHongmin Li
Jun 24, 2008·Antiviral Research·Hongping DongPei-Yong Shi
Aug 22, 2008·Journal of Virology·Stephane DaffisMichael S Diamond
Sep 5, 2008·Journal of Virology·Volker FensterlGanes C Sen

❮ Previous
Next ❯

Citations

Nov 19, 2013·Virologica Sinica·Matthew BrecherHongmin Li
May 28, 2011·Accounts of Chemical Research·Chengqi Yi, Tao Pan
Apr 24, 2012·Cellular & Molecular Immunology·Juan LiuXuetao Cao
Sep 12, 2012·Cell Research·Ganes C Sen, Volker Fensterl
Jun 7, 2011·Nature Immunology·Andreas PichlmairGiulio Superti-Furga
Jun 21, 2011·Nature Immunology·Andrea Ablasser, Veit Hornung
Feb 22, 2012·Nature Immunology·Nan Yan, Zhijian J Chen
Jan 20, 2011·Nature Immunology·Adolfo García-Sastre
Dec 15, 2012·Nature Reviews. Immunology·Michael S Diamond, Michael Farzan
May 29, 2012·Proceedings of the National Academy of Sciences of the United States of America·Mickaël BouvetEtienne Decroly
Apr 11, 2013·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Nancy C Reich
Nov 5, 2013·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Michael ByrnePamela Pavco
Aug 1, 2013·The Journal of Infectious Diseases·Jethro A HerbergMichael Levin
Jul 7, 2011·Antimicrobial Agents and Chemotherapy·Qing-Yin WangPei-Yong Shi
Jun 8, 2012·Journal of Virology·Hillary J Stahla-BeekBrian J Geiss
Jun 7, 2013·Journal of Virology·Hyelim ChoMichael S Diamond
Mar 15, 2013·Journal of Virology·Shi-Hua LiPei-Yong Shi
Jan 20, 2012·Journal of Virology·Søren Jensen, Allan Randrup Thomsen
Sep 3, 2011·Microbiology and Molecular Biology Reviews : MMBR·Denis Gerlier, Douglas S Lyles
Mar 7, 2012·Microbiology and Molecular Biology Reviews : MMBR·Jonathan Maelfait, Rudi Beyaert
Jun 6, 2014·PLoS Neglected Tropical Diseases·Cheng HuangSlobodan Paessler

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
transgenic

Related Concepts

Related Feeds

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.