{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T16:19:53Z","timestamp":1792167593966,"version":"4.4.0"},"reference-count":52,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI165578"],"award-info":[{"award-number":["AI165578"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI182596"],"award-info":[{"award-number":["AI182596"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI191670"],"award-info":[{"award-number":["AI191670"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2025,12,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Gammaherpesviruses infect &gt;90% of adults and are associated with B cell lymphomas. These viruses drive the expansion and differentiation of germinal center B cells to amplify latent viral reservoir and ensure life-long infection of memory B cells. Additionally, infected germinal center B cells seed viral lymphomagenesis. We previously demonstrated that global deficiency of Interferon Regulatory Factor-1 (IRF-1), a classically antiviral transcription factor, results in increased murine gammaherpesvirus-driven germinal center response and latent viral reservoir. In contrast, B cell-specific loss of IRF-1 expression attenuates murine gammaherpesvirus chronic infection and germinal center response. All gammaherpesviruses encode a conserved protein kinase. We previously showed that the murine gammaherpesvirus protein kinase antagonizes the antiviral activity of global IRF-1 expression to support the establishment of chronic infection. Intriguingly, in this study, we show cooperation between the gammaherpesvirus protein kinase and B cell-intrinsic IRF-1 expression that supported optimal establishment of splenic latent viral reservoir and murine gammaherpesvirus-driven germinal center response. Both viral protein kinase and B cell-intrinsic IRF-1 expression supported the survival and proliferation of germinal center B cells during chronic gammaherpesvirus infection. Elevated DNA damage response or Fas\/FasL expression was not observed, failing to account for elevated apoptosis of IRF-1-deficient germinal center B cells. However, B cell-intrinsic IRF-1 deficiency led to decreased MHC-II expression by germinal center B cells during chronic gammaherpesvirus infection. In summary, the results of this study illustrate the critical role of the cell type in defining the functional outcome of the host-viral interaction.<\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>Gammaherpesviruses are highly prevalent pathogens that uniquely target B cells for the establishment of life-long infection. This study demonstrates cooperation between a conserved gammaherpesvirus protein kinase and B cell-intrinsic IRF-1, a classical host antiviral factor. We show that this cooperation is critical to support proliferation and survival of germinal center B cells, a subset of B cells that is latently infected by gammaherpesviruses and is critical for both the establishment of chronic infection and viral lymphomagenesis.<\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.01375-25","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T14:00:17Z","timestamp":1763647217000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["B cell-intrinsic IRF-1 and conserved gammaherpesvirus protein kinase cooperate to promote murine gammaherpesvirus-driven germinal center response and splenic latent reservoir"],"prefix":"10.1128","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9748-247X","authenticated-orcid":false,"given":"Cade 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