Post-translational modifications, including O-GlcNAcylation, play fundamental roles in modulating cellular events, including transcription, signal transduction, and immune signaling. Several molecular targets of O-GlcNAcylation associated with pathogen-induced innate immune responses have been identified; however, the direct regulatory mechanisms linking O-GlcNAcylation with antiviral RIG-I-like receptor signaling are not fully understood. In this study, we found that cellular levels of O-GlcNAcylation decline in response to infection with Sendai virus. We identified a heavily O-GlcNAcylated serine-rich region between amino acids 249–257 of the mitochondrial antiviral signaling protein (MAVS); modification at this site disrupts MAVS aggregation and prevents MAVS-mediated activation and signaling. O-GlcNAcylation of the serine-rich region of MAVS also suppresses its interaction with TRAF3; this prevents IRF3 activation and production of interferon-β. Taken together, these results suggest that O-GlcNAcylation of MAVS may be a master regulatory event that promotes host defense against RNA viruses.
|Journal||Frontiers in Immunology|
|Publication status||Published - 2021 Feb 2|
Bibliographical noteFunding Information:
This research was supported by the National Research Foundation of Korea (NRF). Grants were given to JC from the Korean Government (NRF-2016R1A5A1010764 and NRF-2015M3A9B6073840).
© Copyright © 2021 Seo, Park, Kweon, Kang, Son, Kim, Seo, Kang, Yi, Lee, Kim, Park, Yang and Cho.
All Science Journal Classification (ASJC) codes
- Immunology and Allergy