TY - JOUR
T1 - Vitamin D and the Ability to Produce 1,25(OH)2D Are Critical for Protection from Viral Infection of the Lungs
AU - Arora, Juhi
AU - Patel, Devanshi R.
AU - Nicol, McKayla J.
AU - Field, Cassandra J.
AU - Restori, Katherine H.
AU - Wang, Jinpeng
AU - Froelich, Nicole E.
AU - Katkere, Bhuvana
AU - Terwilliger, Josey A.
AU - Weaver, Veronika
AU - Luley, Erin
AU - Kelly, Kathleen
AU - Kirimanjeswara, Girish S.
AU - Sutton, Troy C.
AU - Cantorna, Margherita T.
N1 - Publisher Copyright:
© 2022 by the authors.
PY - 2022/8
Y1 - 2022/8
N2 - 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.
AB - 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.
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U2 - 10.3390/nu14153061
DO - 10.3390/nu14153061
M3 - Article
C2 - 35893921
AN - SCOPUS:85136492742
SN - 2072-6643
VL - 14
JO - Nutrients
JF - Nutrients
IS - 15
M1 - 3061
ER -