Vitamin D and the Ability to Produce 1,25(OH)2D Are Critical for Protection from Viral Infection of the Lungs

Juhi Arora, Devanshi R. Patel, McKayla J. Nicol, Cassandra J. Field, Katherine H. Restori, Jinpeng Wang, Nicole E. Froelich, Bhuvana Katkere, Josey A. Terwilliger, Veronika Weaver, Erin Luley, Kathleen Kelly, Girish S. Kirimanjeswara, Troy C. Sutton, Margherita T. Cantorna

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Vitamin D supplementation is linked to improved outcomes from respiratory virus infection, and the COVID-19 pandemic renewed interest in understanding the potential role of vitamin D in protecting the lung from viral infections. 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−) wildtype (WT) and D+ and D− Cyp27B1 (Cyp) knockout (KO, cannot produce 1,25(OH)2D) mice were infected with pandemic H1N1. D− WT, D+ Cyp KO, and D− 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.

Original languageEnglish (US)
Article number3061
JournalNutrients
Volume14
Issue number15
DOIs
StatePublished - Aug 2022

All Science Journal Classification (ASJC) codes

  • Food Science
  • Nutrition and Dietetics

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