Influenza A virus targets a cGAS-independent STING pathway that controls enveloped RNA viruses
Christian K. Holm,Stine H. Rahbek,Hans Henrik Gad,Rasmus O. Bak,Martin R. Jakobsen,Zhaozaho Jiang,Anne Louise Hansen,Simon K. Jensen,Chenglong Sun,Martin K. Thomsen,Anders Laustsen,Camilla G. Nielsen,Kasper Severinsen,Yingluo Xiong,Yingluo Xiong,Dara Burdette,Veit Hornung,Robert Jan Lebbink,Mogens Duch,Katherine A. Fitzgerald,Shervin Bahrami,Jakob Giehm Mikkelsen,Rune Hartmann,Søren R. Paludan +23 more
TLDR
A STING-dependent, cGAS-independent pathway important for full interferon production and antiviral control of enveloped RNA viruses, including influenza A virus (IAV), which is targeted by IAV is identified.Abstract:
Stimulator of interferon genes (STING) is known be involved in control of DNA viruses but has an unexplored role in control of RNA viruses. During infection with DNA viruses STING is activated downstream of cGAMP synthase (cGAS) to induce type I interferon. Here we identify a STING-dependent, cGAS-independent pathway important for full interferon production and antiviral control of enveloped RNA viruses, including influenza A virus (IAV). Further, IAV interacts with STING through its conserved hemagglutinin fusion peptide (FP). Interestingly, FP antagonizes interferon production induced by membrane fusion or IAV but not by cGAMP or DNA. Similar to the enveloped RNA viruses, membrane fusion stimulates interferon production in a STING-dependent but cGAS-independent manner. Abolishment of this pathway led to reduced interferon production and impaired control of enveloped RNA viruses. Thus, enveloped RNA viruses stimulate a cGAS-independent STING pathway, which is targeted by IAV.read more
Citations
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The molecular machinery of regulated cell death
TL;DR: The in-depth comprehension of each of these lethal subroutines and their intercellular consequences may uncover novel therapeutic targets for the avoidance of pathogenic cell loss.
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Non-canonical Activation of the DNA Sensing Adaptor STING by ATM and IFI16 Mediates NF-κB Signaling after Nuclear DNA Damage.
Gillian Dunphy,Sinead M. Flannery,Jessica F. Almine,Dympna J. Connolly,Christina Paulus,Kasper L Jønsson,Martin R. Jakobsen,Michael Nevels,Andrew G. Bowie,Leonie Unterholzner +9 more
TL;DR: It is found that keratinocytes and other human cells mount an innate immune response within hours of etoposide-induced DNA damage, which involves the DNA sensing adaptor STING but is independent of the cytosolic DNA receptor cGAS.
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SAMHD1 acts at stalled replication forks to prevent interferon induction
Flavie Coquel,Maria-Joao Silva,Maria-Joao Silva,Hervé Técher,Karina Zadorozhny,Sushma Sharma,Jadwiga Nieminuszczy,Clément Mettling,Elodie Dardillac,Antoine Barthe,Anne-Lyne Schmitz,Alexy Promonet,Alexandra Cribier,Amélie Sarrazin,Wojciech Niedzwiedz,Bernard S. Lopez,Vincenzo Costanzo,Lumir Krejci,Andrei Chabes,Monsef Benkirane,Yea-Lih Lin,Philippe Pasero +21 more
TL;DR: It is shown that SAMHD1 promotes degradation of nascent DNA at stalled replication forks in human cell lines by stimulating the exonuclease activity of MRE11, which activates the ATR–CHK1 checkpoint and allows the forks to restart replication.
Journal ArticleDOI
Attenuation of cGAS-STING Signaling Is Mediated by a p62/SQSTM1-dependent Autophagy Pathway Activated by TBK1
Thaneas Prabakaran,Chiranjeevi Bodda,Chiranjeevi Bodda,Christian Krapp,Bao-Cun Zhang,Maria H Christensen,Chenglong Sun,Line S. Reinert,Yujia Cai,Søren B. Jensen,Morten K Skouboe,Jens R. Nyengaard,Craig B. Thompson,Robert Jan Lebbink,Ganes C. Sen,Geert van Loo,Rikke Nielsen,Masaaki Komatsu,Lene N. Nejsum,Martin R. Jakobsen,Mads Gyrd-Hansen,Søren R. Paludan +21 more
TL;DR: It is reported that STING degradation following activation of the pathway occurs through autophagy and is mediated by p62/SQSTM1, which is phosphorylated by TBK1 to direct ubiquitinated STING to autophagosomes.
Journal ArticleDOI
Crosstalk between Cytoplasmic RIG-I and STING Sensing Pathways.
TL;DR: This review highlights the importance of the crosstalk between retinoic acid inducible gene-I (RIG-I)-mitochondrial antiviral-signaling protein (MAVS) RNA sensing and the cyclic GMP-AMP synthase (cGAS)- stimulator of interferon genes (STING) DNA sensing pathways in potentiating efficient antiviral responses.
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