What is the role of vitamin D in pandemic H1N1 influenza and SARS-CoV-2 infection?

A recent study published in Nutrients found that vitamin D is vital for lung protection from viral infection.

Study: Vitamin D and the Ability to Produce 1,25(OH)2D Are Critical for Protection from Viral Infection of the Lungs. Image Credit: Iryna Imago/Shutterstock
Study: Vitamin D and the Ability to Produce 1,25(OH)2D Are Critical for Protection from Viral Infection of the Lungs. Image Credit: Iryna Imago/Shutterstock

Background

Low vitamin D levels have been associated with poor outcomes following respiratory diseases such as influenza. High-dose vitamin D supplements have been suggested to decrease seasonal flu severity. The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has renewed interest in these supplements for treating coronavirus disease 2019 (COVID-19).

Vitamin D and its active form 1,25-dihydroxy vitamin D (1,25D) have been implicated in antiviral responses. Multiple studies showed that 1,25D and other vitamin D analogs could induce the production of cathelicidin, a host defense peptide, during viral infection. The cathelicidin LL-37 has been shown to bind to and kill influenza and other viruses in vitro. Thus, vitamin D supplementation could target the influenza virus and SARS-CoV-2.

About the study

In the present study, researchers evaluated the effects of vitamin D on the antiviral response in lungs in mice and hamsters. C57BL/6 wildtype mice, K18-hACE2 mice, cytochrome P450 family 27 subfamily b polypeptide 1 (Cyp27B1) knockout (Cyp KO) mice (that do not produce 1,25D) were bred and housed.

Sex- and age-matched mice were given chow or purified diets with (D+) or without vitamin D (D-). Golden Syrian hamsters were maintained on a chow or D- diet and fed corn oil and vitamin D3. Serum samples were obtained to monitor the vitamin D status of animals. Mice and hamsters were infected with the SARS-CoV-2 WA-1/2020 strain.

D+ and D- wildtype and D+ and D- Cyp KO littermates were fed identical diets with or without vitamin D. They were infected with mouse-adapted H1N1 influenza virus. Experiments involving SARS-CoV-2 were performed in biosafety level 3 enhanced (BSL3+) while those with H1N1 were conducted in BSL2+ conditions.

Findings

The authors observed significantly different levels of serum 25-hydroxy vitamin D (25D) between mice fed D+ or D- diet regardless of the mouse genotype (wildtype or Cyp KO). D+ Cyp KO mice had higher levels of 25D than D+ wildtype mice. Respiratory distress was evident in all mice seven days after H1N1 infection, albeit D+ wildtype showed the least distress. D- wildtype and D- Cyp KO mice exhibited elevated symptoms.

One D+ wildtype mice succumbed to infection; mice in D+ or D- KO groups had a lower survival rate (62% in D+ and 57% in D- KO). Lung sections from vitamin D-deficient mice of either genotype showed inflammation even before infection. Alveolar hemorrhage was more prominent at four days post-infection (dpi) in D- Cyp KO mice than in D+ or D- wildtype mice. By 14 dpi, lung sections of D+ or D- Cyp KO and D- wildtype were much severe than D+ wildtype mice.

K18-hACE2 mice were fed a vitamin D-deficient chow and dosed orally with a vehicle (D-), low (D+), or high (D++) dose of vitamin D3 for eight weeks before SARS-CoV-2 infection. Serum 25D levels were significantly higher in D++ mice before infection and at 14 dpi. SARS-CoV-2 nucleocapsid (N) gene expression was the same in D- and D++ mice at 6 dpi.

SARS-CoV-2 infection-induced expression of interferon-beta and -gamma, but not interferon-alpha. Lung histopathology of D++ mice revealed significantly less type II hyperplasia and alveolar remodeling at 14 dpi. In a final set of experiments with mice, the authors found that 1,25D had no effect on survival from a lethal SARS-CoV-2 dose.

There were no significant differences in serum 25D levels between hamsters fed a chow diet and those fed D- diets for four weeks. Therefore, hamsters were fed a D- diet orally with a vehicle (D-) or 8 μg/day of vitamin D (D+) from 14 days before SARS-CoV-2 infection throughout the experiment. Serum 25D levels were significantly higher in D+ hamsters than D- hamsters on the day of infection until 14 dpi.

N gene was detected at 3 dpi in the lungs but not at 6 dpi, and no differences in N gene expression were noted between the lungs of D- and D+ hamsters. Surprisingly, N gene expression was observed in the colon tissues at 3 dpi and 6 dpi, albeit 1000-fold lower than in the lungs. Lung histopathology revealed significantly higher damage on 6 dpi than on 3 dpi.

Conclusions

The study found that vitamin D deficiency caused lung inflammation before viral infection. Vitamin D-deficient mice showed much more severe respiratory symptoms and lung inflammation than vitamin D-sufficient or -supplemented mice upon infection with H1N1 or SARS-CoV-2. D- mice showed significantly higher inflammation than D+ mice upon H1N1 infection. Moreover, high-dose vitamin D3 supplementation protected mice from SARS-CoV-2 infection.

Notably, vitamin D did not affect the expression of the H1N1 membrane (M) gene or SARS-CoV-2 N gene in the lungs of mice and hamsters. Overall, the findings highlighted the vital role of vitamin D and Cyp27B1 in regulating host responses to SARS-CoV-2 and H1N1. Future studies are needed to uncover the mechanism by which antiviral response is regulated by vitamin D.

Journal reference:
Tarun Sai Lomte

Written by

Tarun Sai Lomte

Tarun is a writer based in Hyderabad, India. He has a Master’s degree in Biotechnology from the University of Hyderabad and is enthusiastic about scientific research. He enjoys reading research papers and literature reviews and is passionate about writing.

Citations

Please use one of the following formats to cite this article in your essay, paper or report:

  • APA

    Sai Lomte, Tarun. (2022, August 01). What is the role of vitamin D in pandemic H1N1 influenza and SARS-CoV-2 infection?. News-Medical. Retrieved on August 10, 2022 from https://www.news-medical.net/news/20220801/What-is-the-role-of-vitamin-D-in-pandemic-H1N1-influenza-and-SARS-CoV-2-infection.aspx.

  • MLA

    Sai Lomte, Tarun. "What is the role of vitamin D in pandemic H1N1 influenza and SARS-CoV-2 infection?". News-Medical. 10 August 2022. <https://www.news-medical.net/news/20220801/What-is-the-role-of-vitamin-D-in-pandemic-H1N1-influenza-and-SARS-CoV-2-infection.aspx>.

  • Chicago

    Sai Lomte, Tarun. "What is the role of vitamin D in pandemic H1N1 influenza and SARS-CoV-2 infection?". News-Medical. https://www.news-medical.net/news/20220801/What-is-the-role-of-vitamin-D-in-pandemic-H1N1-influenza-and-SARS-CoV-2-infection.aspx. (accessed August 10, 2022).

  • Harvard

    Sai Lomte, Tarun. 2022. What is the role of vitamin D in pandemic H1N1 influenza and SARS-CoV-2 infection?. News-Medical, viewed 10 August 2022, https://www.news-medical.net/news/20220801/What-is-the-role-of-vitamin-D-in-pandemic-H1N1-influenza-and-SARS-CoV-2-infection.aspx.

Comments

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
Post a new comment
Post
You might also like...
Study shows probability of getting COVID for mask wearers vs. non-mask wearers