RT Journal Article
SR Electronic
T1 Vitamin D and the ability to produce 1,25(OH)<sub>2</sub>D are critical for protection from viral infection of the lungs
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.06.29.498158
DO 10.1101/2022.06.29.498158
A1 Juhi Arora
A1 Devanshi Patel
A1 McKayla J. Nicol
A1 Cassandra J Field
A1 Katherine H. Restori
A1 Jinpeng Wang
A1 Nicole E. Froelich
A1 Bhuvana Katkere
A1 Josey A. Terwilliger
A1 Veronika Weaver
A1 Erin Luley
A1 Kathleen Kelly
A1 Girish S. Kirimanjeswara
A1 Troy C. Sutton
A1 Margherita T. Cantorna
YR 2022
UL http://biorxiv.org/content/early/2022/06/30/2022.06.29.498158.abstract
AB Vitamin D supplementation has been linked to improved outcomes from respiratory virus infection, and the COVID19 pandemic has 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 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 severe acute respiratory syndrome coronavirus-2 (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 sufficient/supplementation reduced inflammation following infections with H1N1 influenza and SARS-CoV-2.Competing Interest StatementThe authors have declared no competing interest.