Virulent Poxviruses Inhibit DNA Sensing by Preventing STING Activation

Journal of Virology
Iliana GeorganaCarlos Maluquer de Motes

Abstract

Cytosolic recognition of DNA has emerged as a critical cellular mechanism of host immune activation upon pathogen invasion. The central cytosolic DNA sensor cGAS activates STING, which is phosphorylated, dimerizes and translocates from the endoplasmic reticulum (ER) to a perinuclear region to mediate IRF-3 activation. Poxviruses are double-stranded DNA viruses replicating in the cytosol and hence likely to trigger cytosolic DNA sensing. Here, we investigated the activation of innate immune signaling by 4 different strains of the prototypic poxvirus vaccinia virus (VACV) in a cell line proficient in DNA sensing. Infection with the attenuated VACV strain MVA activated IRF-3 via cGAS and STING, and accordingly STING dimerized and was phosphorylated during MVA infection. Conversely, VACV strains Copenhagen and Western Reserve inhibited STING dimerization and phosphorylation during infection and in response to transfected DNA and cyclic GMP-AMP, thus efficiently suppressing DNA sensing and IRF-3 activation. A VACV deletion mutant lacking protein C16, thought to be the only viral DNA sensing inhibitor acting upstream of STING, retained the ability to block STING activation. Similar inhibition of DNA-induced STING activation was also ...Continue Reading

References

Nov 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·G Sutter, B Moss
Nov 5, 1997·Nature Biotechnology·R ZuffereyD Trono
Nov 21, 2007·The Journal of General Virology·Christine Meisinger-HenschelJürgen Hausmann
Sep 18, 2008·The Journal of General Virology·Aodhnait S FahyGeoffrey L Smith
Aug 11, 2010·Proceedings of the National Academy of Sciences of the United States of America·Taeil KimYong-Jun Liu
Oct 5, 2010·Nature Immunology·Leonie UnterholznerAndrew G Bowie
Oct 29, 2010·Journal of Virology·Katharine Fagan-Garcia, Michele Barry
Mar 15, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Xing ZhangTomozumi Imamichi
Oct 12, 2012·PLoS Pathogens·Sebastian AguirreAna Fernandez-Sesma
Nov 8, 2012·Proceedings of the National Academy of Sciences of the United States of America·Jeonghyun AhnGlen N Barber
Dec 15, 2012·Nature Immunology·Dara L Burdette, Russell E Vance
Dec 20, 2012·ELife·Brian J FergusonGeoffrey L Smith
Feb 8, 2013·Proceedings of the National Academy of Sciences of the United States of America·Takeshi KondoTaro Kawai
May 28, 2013·Immunity·Delphine GoubauCaetano Reis e Sousa
May 28, 2013·Immunity·Søren R Paludan, Andrew G Bowie
Jun 14, 2013·The Journal of General Virology·Brian J FergusonGeoffrey L Smith
Sep 4, 2013·The Journal of General Virology·Geoffrey L SmithRebecca P Sumner
Oct 8, 2013·PLoS Pathogens·Nicholas E PetersGeoffrey L Smith
Dec 29, 2013·Journal of Virology·Rebecca P SumnerGeoffrey L Smith
Nov 27, 2014·The EMBO Journal·Arun K MankanVeit Hornung
Jan 22, 2015·The Journal of Biological Chemistry·Sarah NeidelStephen C Graham
Jul 23, 2015·Proceedings of the National Academy of Sciences of the United States of America·Zhe MaBlossom Damania
Sep 1, 2015·Cell Host & Microbe·Jian-jun WuFanxiu Zhu
Sep 26, 2015·Science·Laura LauDaniel B Stetson
Jan 27, 2016·Proceedings of the National Academy of Sciences of the United States of America·Guigen ZhangThomas F Schulz

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Citations

Aug 28, 2020·The EMBO Journal·Rebecca P SumnerGreg J Towers
Sep 29, 2020·Frontiers in Immunology·Yue Lu, Leiliang Zhang
Sep 28, 2018·Journal of Virology·Valerie OdonCarlos Maluquer de Motes
Jul 7, 2020·Autophagy·Julia Sanchez-Garrido, Avinash R Shenoy
Feb 11, 2020·Frontiers in Immunology·Iliana Georgana, Carlos Maluquer de Motes
Nov 6, 2018·Journal of Theoretical Biology·Robert W GreggJason E Shoemaker
Aug 11, 2020·Current Opinion in Virology·Mubeen M MosahebMatthias Gromeier
Oct 30, 2020·Frontiers in Immunology·Misbah El-JesrCarlos Maluquer de Motes
Jan 10, 2021·International Journal of Molecular Sciences·Guendalina FroechlichNicola Zambrano
Mar 19, 2021·PLoS Pathogens·Carlos Maluquer de Motes
Nov 7, 2020·Frontiers in Immunology·Richard B KennedyGregory A Poland
May 1, 2019·Biochemistry·Andrew B Dippel, Ming C Hammond

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Methods Mentioned

BETA
transfection
PCR
enzyme-linked immunosorbent assay
ELISA
oncotherapy
FCS
PMA
Transfections

Software Mentioned

GraphPad Prism
Odyssey

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