2. Academic Validation
  3. EGFR core fucosylation, induced by hepatitis C virus, promotes TRIM40-mediated-RIG-I ubiquitination and suppresses interferon-I antiviral defenses

EGFR core fucosylation, induced by hepatitis C virus, promotes TRIM40-mediated-RIG-I ubiquitination and suppresses interferon-I antiviral defenses

  • Nat Commun. 2024 Jan 22;15(1):652. doi: 10.1038/s41467-024-44960-6.
Qiu Pan 1,  Yan Xie 1,  Ying Zhang 1,  Xinqi Guo 1,  Jing Wang 1,  Min Liu 2,  Xiao-Lian Zhang 3 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Virology and Hubei Province Key Laboratory of Allergy and Immunology, and Department of Immunology, Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan, 430071, China.
  • 2 State Key Laboratory of Virology and Hubei Province Key Laboratory of Allergy and Immunology, and Department of Immunology, Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan, 430071, China. mliu@whu.edu.cn.
  • 3 State Key Laboratory of Virology and Hubei Province Key Laboratory of Allergy and Immunology, and Department of Immunology, Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan, 430071, China. zhangxiaolian@whu.edu.cn.
  • 4 Department of Allergy, Zhongnan Hospital of Wuhan University, Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Wuhan University, Wuhan, 430071, China. zhangxiaolian@whu.edu.cn.
PMID: 38253527 DOI: 10.1038/s41467-024-44960-6
Abstract

Aberrant N-glycosylation has been implicated in viral diseases. Alpha-(1,6)-fucosyltransferase (FUT8) is the sole Enzyme responsible for core fucosylation of N-glycans during glycoprotein biosynthesis. Here we find that multiple viral envelope proteins, including Hepatitis C Virus (HCV)-E2, Vesicular stomatitis virus (VSV)-G, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-Spike and human immunodeficiency virus (HIV)-gp120, enhance FUT8 expression and core fucosylation. HCV-E2 manipulates host transcription factor SNAIL to induce FUT8 expression through EGFR-AKT-SNAIL activation. The aberrant increased-FUT8 expression promotes TRIM40-mediated RIG-I K48-ubiquitination and suppresses the Antiviral interferon (IFN)-I response through core fucosylated-EGFR-JAK1-STAT3-RIG-I signaling. FUT8 inhibitor 2FF, N-glycosylation site-specific mutation (Q352AT) of EGFR, and tissue-targeted Fut8 silencing significantly increase Antiviral IFN-I responses and suppress RNA viral replication, suggesting that core fucosylation mediated by FUT8 is critical for Antiviral innate immunity. These findings reveal an immune evasion mechanism in which virus-induced FUT8 suppresses endogenous RIG-I-mediated Antiviral defenses by enhancing core fucosylated EGFR-mediated activation.

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