{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T16:05:27Z","timestamp":1740153927681,"version":"3.37.3"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T00:00:00Z","timestamp":1705276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI050072"],"award-info":[{"award-number":["AI050072"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["T32 AI007496"],"award-info":[{"award-number":["T32 AI007496"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The MHC class I molecule H-2Dk conveys resistance to acute murine CMV infection in both C57L (H-2Dk transgenic) and MA\/My mice. M.H2k\/b mice are on an MA\/My background aside from a C57L-derived region spanning the MHC (Cmv5s), which diminishes this resistance and causes significant spleen histopathology. To hone in on the effector elements within the Cmv5s interval, we generated several Cmv5-recombinant congenic mouse strains and screened them in vivo, allowing us to narrow the phenotype-associated interval &amp;gt;6-fold and segment the genetic mechanism to at least two independent loci within the MHC region. In addition, we sought to further characterize the Cmv5s-associated phenotypes in their temporal appearance and potential direct relationship to viral load. To this end, we found that Cmv5s histopathology and NK cell activation could not be fully mirrored in the MA\/My mice with increased viral dose, and that marginal zone destruction was the first apparent Cmv5s phenotype, being reliably quantified as early as 2 d postinfection in the M.H2k\/b mice, prior to divergence in viral load, weight loss, or NK cell phenotype. Finally, we further dissect NK cell involvement, finding no intrinsic differences in NK cell function, despite increased upregulation of activation markers and checkpoint receptors. In conclusion, these data dissect the genetic and immunologic underpinnings of Cmv5 and reveal a model in which polymorphism within the MHC region of the genome leads to the development of tissue damage and corrupts protective NK cell immunity during acute viral infection.<\/jats:p>","DOI":"10.4049\/jimmunol.2300648","type":"journal-article","created":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T13:24:12Z","timestamp":1705325052000},"page":"813-824","source":"Crossref","is-referenced-by-count":1,"title":["Multiple Immune and Genetic Mechanisms Contribute to <i>Cmv5s<\/i>-Driven Susceptibility and Tissue Damage during Acute Murine Cytomegalovirus Infection"],"prefix":"10.1093","volume":"212","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9026-1691","authenticated-orcid":false,"given":"Jessica L","family":"Annis","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia , Charlottesville VA"},{"name":"Beirne B. Carter Center for Immunology Research, University of Virginia , Charlottesville, VA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John Benjamin W","family":"Duncan","sequence":"additional","affiliation":[{"name":"Biomedical Sciences Graduate Program, School of Medicine, University of Virginia , Charlottesville, VA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7703-5455","authenticated-orcid":false,"given":"Helen O","family":"Billcheck","sequence":"additional","affiliation":[{"name":"Center for Comparative Medicine, School of Medicine, University of Virginia , Charlottesville, VA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6872-3043","authenticated-orcid":false,"given":"Anna G","family":"Kuzma","sequence":"additional","affiliation":[{"name":"Beirne B. Carter Center for Immunology Research, University of Virginia , Charlottesville, VA"},{"name":"Division of Nephrology, Department of Medicine, University of Virginia , Charlottesville, VA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rowena B","family":"Crittenden","sequence":"additional","affiliation":[{"name":"Beirne B. Carter Center for Immunology Research, University of Virginia , Charlottesville, VA"},{"name":"Division of Nephrology, Department of Medicine, University of Virginia , Charlottesville, VA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2872-7685","authenticated-orcid":false,"given":"Michael G","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia , Charlottesville VA"},{"name":"Beirne B. Carter Center for Immunology Research, University of Virginia , Charlottesville, VA"},{"name":"Division of Nephrology, Department of Medicine, University of Virginia , Charlottesville, VA"},{"name":"Center for Immunity, Inflammation, and Regenerative Medicine, University of Virginia , Charlottesville, VA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,1,15]]},"reference":[{"key":"2025020405455026200_r1","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1146\/annurev-genet-120116-023425","article-title":"Human genetic determinants of viral diseases","volume":"51","author":"Kenney","year":"2017","journal-title":"Annu. Rev. Genet."},{"key":"2025020405455026200_r2","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1146\/annurev.immunol.23.021704.115526","article-title":"NK cell recognition","volume":"23","author":"Lanier","year":"2005","journal-title":"Annu. Rev. 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