O-GlcNAcylation of SAMHD1 Indicating a Link between Metabolic Reprogramming and Anti-HBV Immunity

Hu, J.; Gao, Q.; Yang, Y.; Xia, J.; Zhang, W.; Chen, Y.; Zhou, Z.; Chang, L.; Hu, Y.; Zhou, H.; Liang, L.; Li, X.; Long, Q.; Wang, K.; Huang, A.; Tang, N.

doi:10.1101/2020.03.09.983338

bioRxiv · 10.1101/2020.03.09.983338

O-GlcNAcylation of SAMHD1 Indicating a Link between Metabolic Reprogramming and Anti-HBV Immunity

Hu, J.·Gao, Q.·Yang, Y.·Xia, J.·Zhang, W.·Chen, Y.·Zhou, Z.·Chang, L.·Hu, Y.·Zhou, H.·Liang, L.·Li, X.·Long, Q.·Wang, K.·Huang, A.·Tang, N.

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Abstract

Viruses hijack the host cell machinery to promote viral replication; however, the mechanism by which metabolic reprogramming regulates innate antiviral immunity in the host remains elusive. Herein, we found that Hepatitis B virus (HBV) infection upregulates glucose transporter 1expression, promotes hexosamine biosynthesis pathway (HBP) activity, and enhances O-linked {beta}-N-acetylglucosamine (O-GlcNAc) modification of downstream proteins. HBP-mediated O-GlcNAcylation positively regulates host antiviral response against HBV in vitro and in vivo. Mechanistically, O-GlcNAc transferase (OGT)-mediated O-GlcNAcylation of sterile alpha motif and histidine/aspartic acid domain-containing protein 1 (SAMHD1) on Ser93 stabilizes SAMHD1 and enhances its antiviral activity. In addition, O-GlcNAcylation of SAMHD1 promoted its antiviral activity against human immunodeficiency virus-1 in vitro. In conclusion, the results of our study reveal a link between HBP, O-GlcNAc modification, and innate antiviral immunity by targeting SAMHD1. Therefore, the results of this study demonstrate a strategy for the potential treatment of HBV infection by modulating HBP activity.

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Hu, J., Gao, Q., Yang, Y., Xia, J., Zhang, W., Chen, Y., Zhou, Z., Chang, L., Hu, Y., Zhou, H., Liang, L., Li, X., Long, Q., Wang, K., Huang, A., Tang, N.. 2020-03-13. O-GlcNAcylation of SAMHD1 Indicating a Link between Metabolic Reprogramming and Anti-HBV Immunity. https://doi.org/10.1101/2020.03.09.983338

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