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.
All data generated or analysed during this study are included in the manuscript and supporting files.
- Marc S Horwitz
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: All work was approved by the Animal Care Committee (ACC) of the University of British504 Columbia (Protocols A17- 0105, A17-0184).
- Dario Riccardo Valenzano, Max Planck Institute for Biology of Ageing, Germany
- Received: January 29, 2021
- Accepted: May 31, 2021
- Accepted Manuscript published: June 3, 2021 (version 1)
© 2021, Mouat et al.
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