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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,3,24]]},"abstract":"<jats:p>\n                    Allelic variation can impact viral clearance and disease severity. Still, our understanding of the effect of the autoimmunity-associated allelic variant of\n                    <jats:italic toggle=\"yes\">Ptpn22<\/jats:italic>\n                    (PEP-R619W) on antiviral immunity remains incomplete, as previous reports have only focused on chronic lymphocytic choriomeningitis virus infection. This research defines how the loss of\n                    <jats:italic toggle=\"yes\">Ptpn22<\/jats:italic>\n                    (PEP-null) and PEP-R619W changes antiviral immunity during an acute coronavirus infection. We address the hypothesis that CRISPR\/Cas9-generated PEP-null and PEP-R619W mice have enhanced antiviral immunity over PEP-wild-type (WT) mice during coronavirus infection. Following mouse hepatitis virus A59 infection, we interrogated pathology, cytokine production, and cellular responses in the blood, spleen, and liver of PEP-WT, PEP-null, and PEP-R619W mice. Key findings show that PEP-R619W mice have reduced viral titer and weight loss, increased survival, and more mature natural killer (NK) cells in the liver and spleen compared to PEP-WT mice. Interestingly, protection against disease in PEP-null mice was inoculation dose dependent, whereas PEP-R619W conferred immunity regardless of infection dose. Further, Rag1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    PEP-R619W mice had increased survival and reduced viral titer over Rag1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    PEP-WT mice. PEP-R619W mice also had higher concentrations of interferon-gamma (IFN\u03b3) and enhanced IFN\u03b3 production by mature NK cells in the liver at 3 d postinfection. Finally, NK cell depletion elevated PEP-R619W viral titer to similar levels as PEP-WT mice. This study investigates the role of\n                    <jats:italic toggle=\"yes\">Ptpn22<\/jats:italic>\n                    within NK cells and demonstrates that the\n                    <jats:italic toggle=\"yes\">Ptpn22<\/jats:italic>\n                    allelic variant augments NK cell function and is beneficial during coronavirus infection.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2519903123","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T17:40:47Z","timestamp":1773855647000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1,"title":["An autoimmunity-associated allele of\n                    <i>PTPN22<\/i>\n                    enhances innate antiviral immunity to protect against acute coronavirus infection"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1956-7814","authenticated-orcid":false,"given":"Alec M.","family":"Bevis","sequence":"first","affiliation":[{"name":"Department of Molecular Biosciences, University of Kansas","place":["Lawrence"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1179-6214","authenticated-orcid":false,"given":"Kathryn J. 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