ArticlePLoS pathogens2017
GP73 represses host innate immune response to promote virus replication by facilitating MAVS and TRAF6 degradation.
Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 55 citations in OpenAlex.
- The E3 ligase ASB3 downregulates antiviral innate immunity by targeting MAVS for ubiquitin-proteasomal degradation.Cell death and differentiation · 2024Article
- Advances in drug-induced liver injury research: in vitro models, mechanisms, omics and gene modulation techniques.Cell & bioscience · 2024Review
- ZIKV induces P62-mediated autophagic degradation of TRAF6 through TRAF6-NS1 interaction.iScience · 2024Article
- Article
- Golgi protein 73: the driver of inflammation in the immune and tumor microenvironment.Frontiers in immunology · 2024Review
- Golgi protein 73: charting new territories in diagnosing significant fibrosis in MASLD: a prospective cross-sectional study.Frontiers in endocrinology · 2024Article
- Epstein-Barr Virus Envelope Glycoprotein gp110 Inhibits IKKi-Mediated Activation of NF-κB and Promotes the Degradation of β-Catenin.Microbiology spectrum · 2023Article
- Hepatitis B virus promotes hepatocellular carcinoma development by activating GP73 to repress the innate immune response.Infectious agents and cancer · 2022Article
- MicroRNA-200c-targeted contactin 1 facilitates the replication of influenza A virus by accelerating the degradation of MAVS.PLoS pathogens · 2022Article
- GOLM1 is related to the inflammatory/immune nature of uveal melanoma and acts as a promising indicator for prognosis and immunotherapy response.Frontiers in genetics · 2022Article
- GP73 is a glucogenic hormone contributing to SARS-CoV-2-induced hyperglycemia.Nature metabolism · 2022Article
- Development of an Eight-gene Prognostic Model for Overall Survival Prediction in Patients with Hepatocellular Carcinoma.Journal of clinical and translational hepatology · 2021Article
- Regulation of antiviral innate immune signaling and viral evasion following viral genome sensing.Experimental & molecular medicine · 2021Review
- The RNA binding protein Quaking represses splicing of the Fibronectin EDA exon and downregulates the interferon response.Nucleic acids research · 2021Article
- Role of Mitochondria in Viral Infections.Life (Basel, Switzerland) · 2021Review
- Caprine MAVS Is a RIG-I Interacting Type I Interferon Inducer Downregulated by Peste des Petits Ruminants Virus Infection.Viruses · 2021Article
- DDIT3 Targets Innate Immunity via the DDIT3-OTUD1-MAVS Pathway To Promote Bovine Viral Diarrhea Virus Replication.Journal of virology · 2021Article
- MAVS: A Two-Sided CARD Mediating Antiviral Innate Immune Signaling and Regulating Immune Homeostasis.Frontiers in microbiology · 2021Review
- Golgi Phosphoprotein 73: The Driver of Epithelial-Mesenchymal Transition in Cancer.Frontiers in oncology · 2021Review
- Grass Carp Reovirus VP35 Degrades MAVS Through the Autophagy Pathway to Inhibit Fish Interferon Production.Frontiers in immunology · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatitis C virus (HCV) infection is a leading cause of chronic liver diseases and hepatocellular carcinoma (HCC) and Golgi protein 73 (GP73) is a serum biomarker for liver diseases and HCC. However, the mechanism underlying GP73 regulates HCV infection is largely unknown. Here, we revealed that GP73 acts as a novel negative regulator of host innate immunity to facilitate HCV infection. GP73 expression is activated and correlated with interferon-beta (IFN-β) production during HCV infection in patients' serum, primary human hepatocytes (PHHs) and human hepatoma cells through mitochondrial antiviral signaling protein (MAVS), TNF receptor-associated factor 6 (TRAF6) and mitogen-activated protein kinase kinase/extracellular regulated protein kinase (MEK/ERK) pathway. Detailed studies revealed that HCV infection activates MAVS that in turn recruits TRAF6 via TRAF-interacting-motifs (TIMs), and TRAF6 subsequently directly recruits GP73 to MAVS via coiled-coil domain. After binding with MAVS and TRAF6, GP73 promotes MAVS and TRAF6 degradation through proteasome-dependent pathway. Moreover, GP73 attenuates IFN-β promoter, IFN-stimulated response element (ISRE) and nuclear factor κB (NF-κB) promoter and down-regulates IFN-β, IFN-λ1, interleukin-6 (IL-6) and IFN-stimulated gene 56 (ISG56), leading to the repression of host innate immunity. Finally, knock-down of GP73 down-regulates HCV infection and replication in Huh7-MAVSR cells and primary human hepatocytes (PHHs), but such repression is rescued by GP73m4 (a mutant GP73 resists to GP73-shRNA#4) in Huh7-MAVSR cells, suggesting that GP73 facilitates HCV infection. Taken together, we demonstrated that GP73 acts as a negative regulator of innate immunity to facilitate HCV infection by interacting with MAVS/TRAF6 and promoting MAVS/TRAF6 degradation. This study provides new insights into the mechanism of HCV infection and pathogenesis, and suggests that GP73 is a new potential antiviral target in the prevention and treatment of HCV associated diseases.
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