1. Immunology and Inflammation
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Latent gammaherpesvirus exacerbates arthritis through modification of age-associated B cells

  1. Isobel C Mouat
  2. Zachary J Morse
  3. Iryna Shanina
  4. Kelly L Brown
  5. Marc S Horwitz  Is a corresponding author
  1. University of British Columbia, Canada
Research Article
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Cite this article as: eLife 2021;10:e67024 doi: 10.7554/eLife.67024

Abstract

Epstein-Barr virus (EBV) infection is associated with rheumatoid arthritis (RA) in adults, though the nature of the relationship remains unknown. Herein, we examine the contribution of viral infection to the severity of arthritis in mice. We provide the first evidence that latent gammaherpesvirus infection enhances clinical arthritis, modeling EBV's role in RA. Mice latently infected with a murine analog of EBV, gammaherpesvirus 68 (gHV68), develop more severe collagen-induced arthritis and a Th1-skewed immune profile reminiscent of human disease. We demonstrate that disease enhancement requires viral latency and is not due to active virus stimulation of the immune response. Age-associated B cells (ABCs) are associated with several human autoimmune diseases, including arthritis, though their contribution to disease is not well understood. Using ABC knockout mice, we provide the first evidence that ABCs are mechanistically required for viral enhancement of disease, thereby establishing that ABCs are impacted by latent gammaherpesvirus infection and provoke arthritis.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Isobel C Mouat

    Microbiology and Immunology, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
  2. Zachary J Morse

    Microbiology and Immunology, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
  3. Iryna Shanina

    Microbiology and Immunology, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
  4. Kelly L Brown

    2Department of Pediatrics, Division of Rheumatology, and British Columbia Children's Hospital 8 Research Institute, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
  5. Marc S Horwitz

    Microbiology and Immunology, University of British Columbia, Vancouver, Canada
    For correspondence
    mhorwitz@mail.ubc.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5922-2199

Funding

Multiple Sclerosis Society of Canada (# 3070)

  • Marc S Horwitz

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All work was approved by the Animal Care Committee (ACC) of the University of British504 Columbia (Protocols A17- 0105, A17-0184).

Reviewing Editor

  1. Dario Riccardo Valenzano, Max Planck Institute for Biology of Ageing, Germany

Publication history

  1. Received: January 29, 2021
  2. Accepted: May 31, 2021
  3. Accepted Manuscript published: June 3, 2021 (version 1)

Copyright

© 2021, Mouat et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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