Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

STING controls Herpes Simplex Virus in vivo independent of type I interferon induction

Lívia H. Yamashiro, Stephen C. Wilson, Huntly M. Morrison, Vasiliki Karalis, Jing-Yi J. Chung, Katherine J. Chen, Helen S. Bateup, View ORCID ProfileMoriah L. Szpara, Angus Y. Lee, Jeffery S. Cox, Russell E. Vance
doi: https://doi.org/10.1101/2019.12.12.874792
Lívia H. Yamashiro
1Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720 USA
2Howard Hughes Medical Institute, University of California, Berkeley, CA 94720 USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stephen C. Wilson
1Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720 USA
3Celgene Corporation, 200 Cambridge park Dr, Cambridge, MA 02140
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Huntly M. Morrison
1Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720 USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vasiliki Karalis
4Division of Neurobiology, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720 USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jing-Yi J. Chung
1Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720 USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Katherine J. Chen
1Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720 USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Helen S. Bateup
4Division of Neurobiology, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720 USA
5Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720 USA
6Chan Zuckerberg Biohub, San Francisco, CA 94158 USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Moriah L. Szpara
7Department of Biochemistry and Molecular Biology, Center for Infectious Disease Dynamics, Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA 16801 USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Moriah L. Szpara
Angus Y. Lee
8Cancer Research Laboratory, University of California, Berkeley, CA 94720 USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jeffery S. Cox
1Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720 USA
9Henry Wheeler Center for Emerging and Neglected Diseases, University of California, Berkeley, CA 94720 USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Russell E. Vance
1Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720 USA
2Howard Hughes Medical Institute, University of California, Berkeley, CA 94720 USA
8Cancer Research Laboratory, University of California, Berkeley, CA 94720 USA
9Henry Wheeler Center for Emerging and Neglected Diseases, University of California, Berkeley, CA 94720 USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: rvance@berkeley.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

The Stimulator of Interferon Genes (STING) pathway initiates potent immune responses upon recognition of DNA derived from bacteria, viruses and tumors. To signal, the C-terminal tail (CTT) of STING recruits TBK1, a kinase that phosphorylates serine 365 (S365) in the CTT. Phospho-S365 acts as a docking site for IRF3, a transcription factor that is phosphorylated and activated by TBK1, leading to transcriptional induction of type I interferons (IFNs). IFNs are essential for antiviral immunity and are widely viewed as the primary output of STING signaling in mammals. However, other more evolutionarily ancestral responses, such as induction of NF-κB or autophagy, also occur downstream of STING. The relative importance of the various outputs of STING signaling during in vivo infections is unclear. Here we report that mice harboring a serine 365-to-alanine (S365A) point mutation in STING exhibit normal susceptibility to Mycobacterium tuberculosis infection but, unexpectedly, are resistant to Herpes Simplex Virus (HSV)-1, despite lacking STING-induced type I IFN responses. Likewise, we find Irf3-/- mice exhibit resistance to HSV-1. By contrast, resistance to HSV-1 is abolished in mice lacking the STING CTT or TBK1, suggesting that STING protects against HSV-1 upon TBK1 recruitment by the STING CTT, independent of IRF3 or type I IFNs. Interestingly, we find that STING-induced autophagy is a TBK1-dependent IRF3-independent process that is conserved in the STING S365A mice, and autophagy has previously been shown to be required for resistance to HSV-1. We thus propose that autophagy and perhaps other ancestral interferon-independent functions of STING are required for STING-dependent antiviral responses in vivo.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted December 13, 2019.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
STING controls Herpes Simplex Virus in vivo independent of type I interferon induction
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
STING controls Herpes Simplex Virus in vivo independent of type I interferon induction
Lívia H. Yamashiro, Stephen C. Wilson, Huntly M. Morrison, Vasiliki Karalis, Jing-Yi J. Chung, Katherine J. Chen, Helen S. Bateup, Moriah L. Szpara, Angus Y. Lee, Jeffery S. Cox, Russell E. Vance
bioRxiv 2019.12.12.874792; doi: https://doi.org/10.1101/2019.12.12.874792
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
STING controls Herpes Simplex Virus in vivo independent of type I interferon induction
Lívia H. Yamashiro, Stephen C. Wilson, Huntly M. Morrison, Vasiliki Karalis, Jing-Yi J. Chung, Katherine J. Chen, Helen S. Bateup, Moriah L. Szpara, Angus Y. Lee, Jeffery S. Cox, Russell E. Vance
bioRxiv 2019.12.12.874792; doi: https://doi.org/10.1101/2019.12.12.874792

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Immunology
Subject Areas
All Articles
  • Animal Behavior and Cognition (3477)
  • Biochemistry (7316)
  • Bioengineering (5294)
  • Bioinformatics (20189)
  • Biophysics (9972)
  • Cancer Biology (7697)
  • Cell Biology (11243)
  • Clinical Trials (138)
  • Developmental Biology (6416)
  • Ecology (9911)
  • Epidemiology (2065)
  • Evolutionary Biology (13271)
  • Genetics (9347)
  • Genomics (12544)
  • Immunology (7667)
  • Microbiology (18928)
  • Molecular Biology (7415)
  • Neuroscience (40870)
  • Paleontology (298)
  • Pathology (1226)
  • Pharmacology and Toxicology (2125)
  • Physiology (3138)
  • Plant Biology (6836)
  • Scientific Communication and Education (1268)
  • Synthetic Biology (1891)
  • Systems Biology (5295)
  • Zoology (1083)