{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T20:32:02Z","timestamp":1793133122467,"version":"4.5.0"},"reference-count":49,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"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":["AI191670"],"award-info":[{"award-number":["AI191670"]}],"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":["AI194704"],"award-info":[{"award-number":["AI194704"]}],"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":["AI165578, AI182596"],"award-info":[{"award-number":["AI165578, AI182596"]}],"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":[[2026,9,22]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Gammaherpesviruses are prevalent pathogens that are associated with cancers and autoimmune diseases. All gammaherpesviruses encode a conserved protein kinase. Expression of orf36, the protein kinase encoded by murine gammaherpesvirus 68 (MHV68), supports the establishment of a latent viral reservoir in splenic B cells\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      . Specifically, orf36 antagonizes myeloid cell-intrinsic STAT1 function to support the passage of MHV68 from myeloid cells to splenic B cells. STAT1 is a ubiquitously expressed transcription factor and a critical effector of interferon (IFN) antiviral functions. To define the extent to which the observed orf36-STAT1 antagonism reflected orf36 antagonism of the type I IFN axis, this study employed mouse models of myeloid cell-specific type I IFN receptor (IFNAR1) or interferon regulatory factor 3 (IRF-3) deficiencies. Myeloid cell-specific IFNAR1 deficiency resulted in the rescue of the attenuated splenic latent reservoir of the orf36 null MHV68, similar to that observed upon myeloid cell-specific STAT1 deficiency, refining the viral antagonism of the IFNAR1-STAT1 axis. However, and unlike that observed for IFNAR1, myeloid cell-specific deficiency of IRF-3, the transcription factor that drives type I IFN expression, failed to affect the attenuated chronic infection of the orf36 null MHV68 mutant. Unexpectedly, wild-type MHV68 reactivation in the spleen was attenuated in mice with myeloid cell-specific IRF-3 deficiency. Thus, the current study highlights a myeloid cell-specific antagonism between conserved gammaherpesvirus protein kinase and type I IFN receptor and unveils an intriguing proviral role of myeloid-specific IRF-3 expression during chronic gammaherpesvirus infection.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        This study focuses on defining the mechanisms by which conserved gammaherpesvirus protein kinase facilitates establishment of chronic infection\n                        <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                        . We previously demonstrated that the viral protein kinase antagonizes STAT1 function in myeloid cells to allow gammaherpesvirus passage from myeloid cells to B cells in the spleen. Using a combination of virus and host genetics, this study demonstrates that the previously observed antagonism between viral protein kinase and STAT1 is at least in part due to antagonism of type I interferon (IFN) signaling. Despite the well-established role of IRF-3 in type I IFN expression, myeloid cell-specific IRF-3 deficiency failed to rescue attenuated chronic infection of viral kinase null gammaherpesvirus. Unexpectedly, splenic reactivation of wild-type gammaherpesvirus was decreased in mice with myeloid cell-specific IRF-3 deficiency, unveiling a proviral role of IRF-3 expressed by myeloid cells during chronic gammaherpesvirus infection.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.01110-26","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T14:38:56Z","timestamp":1788273536000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Conserved gammaherpesvirus protein kinase counters myeloid cell-specific type I IFN receptor but not IRF-3 expression to promote the establishment of chronic latent infection in the spleen"],"prefix":"10.1128","volume":"100","author":[{"given":"Erika R.","family":"Johansen","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00qqv6244","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Medical College of Wisconsin","place":["Milwaukee, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0617-6904","authenticated-orcid":false,"given":"Matthew A.","family":"Brown","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00qqv6244","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Medical College of Wisconsin","place":["Milwaukee, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xander G.","family":"Bradeen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00qqv6244","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Medical College of Wisconsin","place":["Milwaukee, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cade R.","family":"Rahlf","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00qqv6244","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Medical College of Wisconsin","place":["Milwaukee, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Avila","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00qqv6244","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Medical College of Wisconsin","place":["Milwaukee, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damon. L.","family":"Schmalzriedt","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00qqv6244","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Medical College of Wisconsin","place":["Milwaukee, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9499-088X","authenticated-orcid":true,"given":"Vera L.","family":"Tarakanova","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00qqv6244","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Medical College of Wisconsin","place":["Milwaukee, USA"]},{"name":"Cancer Center, Medical College of Wisconsin","place":["Milwaukee, 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