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

Y-RNAs Lead an Endogenous Program of RIG-I Agonism Mobilized upon RNA Virus Infection and Targeted by HIV

Nicolas Vabret, Valérie Najburg, Alexander Solovyov, Petr Šulc, Sreekumar Balan, Guillaume Beauclair, Maxime Chazal, Hugo Varet, Rachel Legendre, Odile Sismeiro, Raul Y. Sanchez David, Christopher McClain, Ramya Gopal, Lise Chauveau, Olivier Schwartz, Nolwenn Jouvenet, Martin Markowitz, Frédéric Tangy, Nina Bhardwaj, Benjamin D. Greenbaum, Anastasia V. Komarova
doi: https://doi.org/10.1101/773820
Nicolas Vabret
1Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
2Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
10Department of Medicine, Hematology and Medical Oncology, Department of Oncological Sciences, Department of Pathology, Center for Computational Immunology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: nicolas.vabret@mssm.edu nicolas.vabret@mssm.edu
Valérie Najburg
3Viral Genomics and Vaccination Unit, Department of Virology, Institut Pasteur, CNRS UMR-3569, 75015 Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alexander Solovyov
1Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
2Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
10Department of Medicine, Hematology and Medical Oncology, Department of Oncological Sciences, Department of Pathology, Center for Computational Immunology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
11Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: nicolas.vabret@mssm.edu benjamin.greenbaum@mssm.edu
Petr Šulc
4Center for Molecular Design and Biomimetics at the Biodesign Institute and School of Molecular Sciences, Arizona State University, Tempe, Arizona 85287, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sreekumar Balan
1Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
2Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
10Department of Medicine, Hematology and Medical Oncology, Department of Oncological Sciences, Department of Pathology, Center for Computational Immunology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: nicolas.vabret@mssm.edu
Guillaume Beauclair
3Viral Genomics and Vaccination Unit, Department of Virology, Institut Pasteur, CNRS UMR-3569, 75015 Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Maxime Chazal
3Viral Genomics and Vaccination Unit, Department of Virology, Institut Pasteur, CNRS UMR-3569, 75015 Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hugo Varet
5Transcriptome and EpiGenome platform, BioMics, Center of Innovation and Technological Research, Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France
6Hub informatique et Biostatistique, Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI, USR 3756 IP-CNRS), Institut Pasteur, 28 Rue du Docteur Roux, 75724 Paris Cedex 15, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rachel Legendre
5Transcriptome and EpiGenome platform, BioMics, Center of Innovation and Technological Research, Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France
6Hub informatique et Biostatistique, Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI, USR 3756 IP-CNRS), Institut Pasteur, 28 Rue du Docteur Roux, 75724 Paris Cedex 15, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Odile Sismeiro
5Transcriptome and EpiGenome platform, BioMics, Center of Innovation and Technological Research, Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Raul Y. Sanchez David
3Viral Genomics and Vaccination Unit, Department of Virology, Institut Pasteur, CNRS UMR-3569, 75015 Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christopher McClain
1Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
2Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
10Department of Medicine, Hematology and Medical Oncology, Department of Oncological Sciences, Department of Pathology, Center for Computational Immunology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: nicolas.vabret@mssm.edu
Ramya Gopal
1Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
2Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
10Department of Medicine, Hematology and Medical Oncology, Department of Oncological Sciences, Department of Pathology, Center for Computational Immunology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: nicolas.vabret@mssm.edu
Lise Chauveau
7Virus & Immunity Unit, Department of Virology, Institut Pasteur, CNRS UMR-3569, 75015 Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Olivier Schwartz
7Virus & Immunity Unit, Department of Virology, Institut Pasteur, CNRS UMR-3569, 75015 Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nolwenn Jouvenet
3Viral Genomics and Vaccination Unit, Department of Virology, Institut Pasteur, CNRS UMR-3569, 75015 Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Martin Markowitz
8Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Frédéric Tangy
3Viral Genomics and Vaccination Unit, Department of Virology, Institut Pasteur, CNRS UMR-3569, 75015 Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nina Bhardwaj
1Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
2Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
9Parker Institute of Cancer Immunotherapy, USA
10Department of Medicine, Hematology and Medical Oncology, Department of Oncological Sciences, Department of Pathology, Center for Computational Immunology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: nicolas.vabret@mssm.edu
Benjamin D. Greenbaum
1Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
2Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
10Department of Medicine, Hematology and Medical Oncology, Department of Oncological Sciences, Department of Pathology, Center for Computational Immunology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
11Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: nicolas.vabret@mssm.edu benjamin.greenbaum@mssm.edu
Anastasia V. Komarova
3Viral Genomics and Vaccination Unit, Department of Virology, Institut Pasteur, CNRS UMR-3569, 75015 Paris, France
12Viral Genomics and Vaccination Unit, Department of Virology, Institut Pasteur, CNRS UMR-3569, 75015 Paris, France.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: anastasia.komarova@pasteur.fr
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

Pattern recognition receptors (PRRs) protect against host invasion by detecting specific molecular patterns found in pathogens and initiating an immune response. While microbial-derived PRR ligands have been extensively characterized, the contribution and relevance of endogenous ligands to PRR activation during viral infection remain overlooked. In this work, we characterize the landscape of endogenous ligands that engage RIG-I-like receptors (RLRs) upon infection by a positive-sense RNA virus, a negative-sense RNA virus or a retrovirus. We found that several endogenous RNAs transcribed by RNA polymerase 3 (Pol3) specifically engage RLRs, and in particular the family of small non-coding repeats Y-RNAs, which presents the highest affinity as RIG-I ligands. We show that this recognition is dependent on Y-RNA mimicking viral secondary structure and its 5’-triphosphate extremity. Further, we found that HIV-1 infection triggers a VPR-dependent downregulation of RNA triphosphatase DUSP11 in vitro and in vivo, leading to an increase of Y-RNA 5’-triphosphorylation that enables their immunogenicity. Importantly, we show that altering DUSP11 expression is sufficient to induce a type-I interferon and T cell activation transcriptional program associated with HIV-1 infection. Overall, our work uncovers the critical contribution of endogenous repeat RNAs ligands to antiviral immunity and demonstrates the role of this pathway in HIV-1 infection.

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 September 18, 2019.
Download PDF

Supplementary Material

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.
Y-RNAs Lead an Endogenous Program of RIG-I Agonism Mobilized upon RNA Virus Infection and Targeted by HIV
(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
Y-RNAs Lead an Endogenous Program of RIG-I Agonism Mobilized upon RNA Virus Infection and Targeted by HIV
Nicolas Vabret, Valérie Najburg, Alexander Solovyov, Petr Šulc, Sreekumar Balan, Guillaume Beauclair, Maxime Chazal, Hugo Varet, Rachel Legendre, Odile Sismeiro, Raul Y. Sanchez David, Christopher McClain, Ramya Gopal, Lise Chauveau, Olivier Schwartz, Nolwenn Jouvenet, Martin Markowitz, Frédéric Tangy, Nina Bhardwaj, Benjamin D. Greenbaum, Anastasia V. Komarova
bioRxiv 773820; doi: https://doi.org/10.1101/773820
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Y-RNAs Lead an Endogenous Program of RIG-I Agonism Mobilized upon RNA Virus Infection and Targeted by HIV
Nicolas Vabret, Valérie Najburg, Alexander Solovyov, Petr Šulc, Sreekumar Balan, Guillaume Beauclair, Maxime Chazal, Hugo Varet, Rachel Legendre, Odile Sismeiro, Raul Y. Sanchez David, Christopher McClain, Ramya Gopal, Lise Chauveau, Olivier Schwartz, Nolwenn Jouvenet, Martin Markowitz, Frédéric Tangy, Nina Bhardwaj, Benjamin D. Greenbaum, Anastasia V. Komarova
bioRxiv 773820; doi: https://doi.org/10.1101/773820

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 (3691)
  • Biochemistry (7800)
  • Bioengineering (5678)
  • Bioinformatics (21295)
  • Biophysics (10582)
  • Cancer Biology (8179)
  • Cell Biology (11946)
  • Clinical Trials (138)
  • Developmental Biology (6764)
  • Ecology (10401)
  • Epidemiology (2065)
  • Evolutionary Biology (13874)
  • Genetics (9709)
  • Genomics (13074)
  • Immunology (8150)
  • Microbiology (20020)
  • Molecular Biology (7859)
  • Neuroscience (43070)
  • Paleontology (321)
  • Pathology (1279)
  • Pharmacology and Toxicology (2260)
  • Physiology (3353)
  • Plant Biology (7232)
  • Scientific Communication and Education (1313)
  • Synthetic Biology (2008)
  • Systems Biology (5539)
  • Zoology (1128)