{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:09:45Z","timestamp":1790766585262,"version":"4.1.0"},"reference-count":69,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T00:00:00Z","timestamp":1713139200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH 2 P51OD011104-62"],"award-info":[{"award-number":["NIH 2 P51OD011104-62"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK129881"],"award-info":[{"award-number":["R01DK129881"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL165265"],"award-info":[{"award-number":["R01HL165265"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R35 HL139930"],"award-info":[{"award-number":["R35 HL139930"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["AHA962950"],"award-info":[{"award-number":["AHA962950"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>This study investigates the roles of T, B, and Natural Killer (NK) cells in the pathogenesis of severe COVID-19, utilizing mouse-adapted SARS-CoV-2-MA30 (MA30). To evaluate this MA30 mouse model, we characterized MA30-infected C57BL\/6 mice (B6) and compared them with SARS-CoV-2-WA1 (an original SARS-CoV-2 strain) infected K18-human ACE2 (K18-hACE2) mice. We found that the infected B6 mice developed severe peribronchial inflammation and rapid severe pulmonary edema, but less lung interstitial inflammation than the infected K18-hACE2 mice. These pathological findings recapitulate some pathological changes seen in severe COVID-19 patients. Using this MA30-infected mouse model, we further demonstrate that T and\/or B cells are essential in mounting an effective immune response against SARS-CoV-2. This was evident as Rag2\u2212\/\u2212 showed heightened vulnerability to infection and inhibited viral clearance. Conversely, the depletion of NK cells did not significantly alter the disease course in Rag2\u2212\/\u2212 mice, underscoring the minimal role of NK cells in the acute phase of MA30-induced disease. Together, our results indicate that T and\/or B cells, but not NK cells, mitigate MA30-induced disease in mice and the infected mouse model can be used for dissecting the pathogenesis and immunology of severe COVID-19.<\/jats:p>","DOI":"10.3390\/v16040611","type":"journal-article","created":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T11:53:53Z","timestamp":1713182033000},"page":"611","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Natural Killer Cells Do Not Attenuate a Mouse-Adapted SARS-CoV-2-Induced Disease in Rag2\u2212\/\u2212 Mice"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7111-525X","authenticated-orcid":false,"given":"Calder R","family":"Ellsworth","sequence":"first","affiliation":[{"name":"Division of Comparative Pathology, Tulane National Primate Research Center, Health Sciences Campus, 18703 Three Rivers Road, Covington, LA 70433, USA"},{"name":"Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7950-9288","authenticated-orcid":false,"given":"Chenxiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Comparative Pathology, Tulane National Primate Research Center, Health Sciences Campus, 18703 Three Rivers Road, Covington, LA 70433, USA"},{"name":"Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3302-0759","authenticated-orcid":false,"given":"Alexis R","family":"Katz","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Pediatrics, Center for Translational Research in Infection and Inflammation, Tulane University School of Medicine, New Orleans, LA 70112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Comparative Pathology, Tulane National Primate Research Center, Health Sciences Campus, 18703 Three Rivers Road, Covington, LA 70433, USA"},{"name":"Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Islamuddin","sequence":"additional","affiliation":[{"name":"Division of Comparative Pathology, Tulane National Primate Research Center, Health Sciences Campus, 18703 Three Rivers Road, Covington, LA 70433, USA"},{"name":"Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoran","family":"Yang","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Pediatrics, Center for Translational Research in Infection and Inflammation, Tulane University School of Medicine, New Orleans, LA 70112, USA"},{"name":"Department of Pulmonary Critical Care and Environmental Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9899-997X","authenticated-orcid":false,"given":"Sarah E","family":"Scheuermann","sequence":"additional","affiliation":[{"name":"Division of Comparative Pathology, Tulane National Primate Research Center, Health Sciences Campus, 18703 Three Rivers Road, Covington, LA 70433, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly A","family":"Goff","sequence":"additional","affiliation":[{"name":"Division of Comparative Pathology, Tulane National Primate Research Center, Health Sciences Campus, 18703 Three Rivers Road, Covington, LA 70433, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9332-7891","authenticated-orcid":false,"given":"Nicholas J","family":"Maness","sequence":"additional","affiliation":[{"name":"Division of Comparative Pathology, Tulane National Primate Research Center, Health Sciences Campus, 18703 Three Rivers Road, Covington, LA 70433, USA"},{"name":"Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9616-9414","authenticated-orcid":false,"given":"Robert V","family":"Blair","sequence":"additional","affiliation":[{"name":"Division of Comparative Pathology, Tulane National Primate Research Center, Health Sciences Campus, 18703 Three Rivers Road, Covington, LA 70433, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5151-6304","authenticated-orcid":false,"given":"Jay K","family":"Kolls","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Pediatrics, Center for Translational Research in Infection and Inflammation, Tulane University School of Medicine, New Orleans, LA 70112, USA"},{"name":"Department of Pulmonary Critical Care and Environmental Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9875-983X","authenticated-orcid":false,"given":"Xuebin","family":"Qin","sequence":"additional","affiliation":[{"name":"Division of Comparative Pathology, Tulane National Primate Research Center, Health Sciences Campus, 18703 Three Rivers Road, Covington, LA 70433, USA"},{"name":"Department of Microbiology and Immunology, Tulane University School of Medicine, New 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