AUTHOR=Seo Junghwa , Park Yun Soo , Kweon Tae Hyun , Kang Jingu , Son Seongjin , Kim Han Byeol , Seo Yu Ri , Kang Min Jueng , Yi Eugene C. , Lee Yong-ho , Kim Jin-Hong , Park Boyoun , Yang Won Ho , Cho Jin Won 

TITLE=O-Linked N-Acetylglucosamine Modification of Mitochondrial Antiviral Signaling Protein Regulates Antiviral Signaling by Modulating Its Activity

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.589259

DOI=10.3389/fimmu.2020.589259

ISSN=1664-3224

ABSTRACT=<p>Post-translational modifications, including <italic>O</italic>-GlcNAcylation, play fundamental roles in modulating cellular events, including transcription, signal transduction, and immune signaling. Several molecular targets of <italic>O</italic>-GlcNAcylation associated with pathogen-induced innate immune responses have been identified; however, the direct regulatory mechanisms linking <italic>O</italic>-GlcNAcylation with antiviral RIG-I-like receptor signaling are not fully understood. In this study, we found that cellular levels of <italic>O</italic>-GlcNAcylation decline in response to infection with Sendai virus. We identified a heavily <italic>O</italic>-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. <italic>O</italic>-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 <italic>O</italic>-GlcNAcylation of MAVS may be a master regulatory event that promotes host defense against RNA viruses.</p>