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Therefore, we evaluated the role of vitamin D using animal models of pandemic H1N1 influenza and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. In mice, dietary-induced vitamin D deficiency resulted in lung inflammation that was present prior to infection. Vitamin D sufficient (D+) and deficient (D\u2212) wildtype (WT) and D+ and D\u2212 Cyp27B1 (Cyp) knockout (KO, cannot produce 1,25(OH)2D) mice were infected with pandemic H1N1. D\u2212 WT, D+ Cyp KO, and D\u2212 Cyp KO mice all exhibited significantly reduced survival compared to D+ WT mice. Importantly, survival was not the result of reduced viral replication, as influenza M gene expression in the lungs was similar for all animals. Based on these findings, additional experiments were performed using the mouse and hamster models of SARS-CoV-2 infection. In these studies, high dose vitamin D supplementation reduced lung inflammation in mice but not hamsters. A trend to faster weight recovery was observed in 1,25(OH)2D treated mice that survived SARS-CoV-2 infection. There was no effect of vitamin D on SARS-CoV-2 N gene expression in the lung of either mice or hamsters. Therefore, vitamin D deficiency enhanced disease severity, while vitamin D sufficiency\/supplementation reduced inflammation following infections with H1N1 influenza and SARS-CoV-2.<\/jats:p>","DOI":"10.3390\/nu14153061","type":"journal-article","created":{"date-parts":[[2022,7,27]],"date-time":"2022-07-27T04:59:16Z","timestamp":1658897956000},"page":"3061","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Vitamin D and the Ability to Produce 1,25(OH)2D Are Critical for Protection from Viral Infection of the Lungs"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2356-0559","authenticated-orcid":false,"given":"Juhi","family":"Arora","sequence":"first","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devanshi R.","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"McKayla J.","family":"Nicol","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassandra J.","family":"Field","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine H.","family":"Restori","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinpeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole E.","family":"Froelich","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhuvana","family":"Katkere","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josey A.","family":"Terwilliger","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Weaver","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7619-0793","authenticated-orcid":false,"given":"Erin","family":"Luley","sequence":"additional","affiliation":[{"name":"Animal Diagnostic Laboratory, The Pennsylvania State University, University Park, PA 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Kelly","sequence":"additional","affiliation":[{"name":"Animal Diagnostic Laboratory, The Pennsylvania State University, University Park, PA 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Girish S.","family":"Kirimanjeswara","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7880-4784","authenticated-orcid":false,"given":"Troy C.","family":"Sutton","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margherita T.","family":"Cantorna","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"799709","DOI":"10.3389\/fnut.2021.799709","article-title":"Association Between Vitamin D and Influenza: Meta-Analysis and Systematic Review of Randomized Controlled Trials","volume":"8","author":"Zhu","year":"2021","journal-title":"Front. 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