Vitamin D Supplementation Improves Human Natural Killer Cell Responses to JC Polyomavirus Infection 2261205

Abstract

Abstract Introduction JC polyomavirus (JCPyV) is a DNA virus that causes the rare but often fatal demyelinating disease progressive multifocal leukoencephalopathy (PML) upon reactivation. Reactivation is due to severe immunosuppression. JCPyV infects the kidney tubule epithelium and replicates in renal tissues in most healthy individuals. Vitamin D deficiency is highly prevalent in clinical settings. Studies in renal transplant recipients showed that vitamin D deficiency is associated with increased BK polyomavirus burden; but the role of vitamin D in JCPyV infection is undefined. Vitamin D could exert immunomodulatory effects on immune cells, including human natural killer (NK) cells. NK cell cytotoxicity is key to controlling JCPyV. Methods We sought to determine whether vitamin D could suppress JCPyV replication in organ-specific primary cells and modulate NK cell responses to JCPyV, by co-culturing NK cells with JCPyV-infected primary renal and brain cells. Viral quantification and NK cell functions were assessed by immunochemical staining, intracellular staining, and flow cytometry. Additionally, immunofluorescence was performed on infected target cells, SVGAs, to assess the presence of JCPyV viral proteins after vitamin D treatment in vitro. Results Preliminary data demonstrates that vitamin D may decrease JCPyV viral replication and augment NK cell cytotoxicity. Additionally, vitamin D treatment decreased the amount of JCPyV viral proteins detected in SVGA cells. Conclusion Understanding the role of vitamin D in the context of JCPyV infection and its ability to modulate NK cell responses may offer novel insights into therapeutic approaches for controlling JCPyV infection and reactivation. Funding Source R01NS116278 Topic Categories Viral Immunology (VIR)