Latent gammaherpesvirus exacerbates arthritis through modification of age-associated B cells
- University of British Columbia, Canada
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.
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Author details
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).
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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Latent gammaherpesvirus exacerbates arthritis through modification of age-associated B cells
eLife 10:e67024.
https://doi.org/10.7554/eLife.67024
