Vitamin C Enhances Antiviral Functions of Lung Epithelial Cells

• Main Authors: Trevor Teafatiller, Sudhanshu Agrawal, Gabriela De Robles, Farah Rahmatpanah, Veedamali S. Subramanian, Anshu Agrawal
• Format: Article
• Language: English
• Published: MDPI AG 2021-08-01
• Series: Biomolecules
• Subjects: vitamin C; airway epithelial cells; antiviral responses; ISGs; vitamin C transporters; <i>GULO</i>-KO mice
• Online Access: https://www.mdpi.com/2218-273X/11/8/1148

Vitamin C is well documented to have antiviral functions; however, there is limited information about its effect on airway epithelial cells—the first cells to encounter infections. Here, we examined the effect of vitamin C on human bronchial epithelium transformed with Ad12-SV40 2B (BEAS-2B) cells, and observed that sodium-dependent vitamin C transporter 2 (SVCT2) was the primary vitamin C transporter. Transcriptomic analysis revealed that treating BEAS-2B cells with vitamin C led to a significant upregulation of several metabolic pathways and interferon-stimulated genes (ISGs) along with a downregulation of pathways involved in lung injury and inflammation. Remarkably, vitamin C also enhanced the expression of the viral-sensing receptors retinoic acid-inducible gene 1 (RIG-1) and melanoma differentiation-associated protein 5 (MDA-5), which was confirmed at the protein and functional levels. In addition, the lungs of <span style="font-variant: small-caps;">l</span>-gulono-γ-lactone oxidase knockout (<i>GULO</i>-KO) mice also displayed a marked decrease in these genes compared to wild-type controls. Collectively, our findings indicate that vitamin C acts at multiple levels to exert its antiviral and protective functions in the lungs.