ArticleThe Journal of biological chemistry2016
The Molecular Chaperone GRP78 Contributes to Toll-like Receptor 3-mediated Innate Immune Response to Hepatitis C Virus in Hepatocytes.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 2 of them syntheses that pooled it.
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Who cites it
30 citing papers in PubMed, 2 syntheses or guidelines pooled it, 47 citations in OpenAlex.
- High rates of Treponema pallidum, Neisseria gonorrhoeae, Chlamydia trachomatis, or Trichomonas vaginalis co-infection in people with HIV: a systematic review and meta-analysis.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2025Pooled it
- Pooled it
- TRIM56 Promotes Antiviral Responses Downstream of TLR4.Viruses · 2026Article
- ATG7 Limits Basal Antiviral Gene Expression and Moderately Promotes VSV Replication in Mammalian Non-Immune Cells.Pathogens (Basel, Switzerland) · 2026Article
- GRP78 in human diseases: From molecular chaperone to therapeutic target.Theranostics · 2026Review
- Zinc Acetate Inhibits Hepatitis A Virus Replication: Possible Treatment for Patients with Type A Acute-on-Chronic Liver Failure.Pathogens (Basel, Switzerland) · 2025Article
- Emerging Roles of TRIM56 in Antiviral Innate Immunity.Viruses · 2025Review
- Genetic Conservation and Diversity of SARS-CoV-2 Envelope Gene Across Variants of Concern.Journal of medical virology · 2025Article
- Mechanisms and Assessment of Genotoxicity of Metallic Engineered Nanomaterials in the Human Environment.Biomedicines · 2024Review
- Adult-Onset Still's Disease (AOSD)-On the Basis of Own Cases.Biomedicines · 2024Article
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- Laboratory diagnosis of CNS infections in children due to emerging and re-emerging neurotropic viruses.Pediatric research · 2024Review
- Cytosolic DNA sensors activation of human astrocytes inhibits herpes simplex virus through IRF1 induction.Frontiers in cellular and infection microbiology · 2024Article
- Combination of Taurine and Black Pepper Extract as a Treatment for Cardiovascular and Coronary Artery Diseases.Nutrients · 2023Review
- Article
- Direct interaction of the molecular chaperone GRP78/BiP with the Newcastle disease virus hemagglutinin-neuraminidase protein plays a vital role in viral attachment to and infection of culture cells.Frontiers in immunology · 2023Article
- ARFIP2 Regulates EMT and Autophagy in Hepatocellular Carcinoma in Part Through the PI3K/Akt Signalling Pathway.Journal of hepatocellular carcinoma · 2022Article
- Characterization, Stress Response and Functional Analyses of Giant River Prawn (Animals : an open access journal from MDPI · 2021Article
- Can SARS-CoV-2 Virus Use Multiple Receptors to Enter Host Cells?International journal of molecular sciences · 2021Review
- Role of Host Immune and Inflammatory Responses in COVID-19 Cases with Underlying Primary Immunodeficiency: A Review.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2020Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Toll-like receptor-3 (TLR3) senses double-stranded RNA intermediates produced during hepatitis C virus (HCV) replication, leading to activation of interferon regulatory factor-3 (IRF3) and NF-κB and subsequent antiviral and proinflammatory responses. Yet, how this TLR3-dependent pathway operates in hepatocytes is unclear. Upon fractionating cultured hepatocytes into various cellular organelles, we observed that TLR3 predominantly resides in endolysosomes of hepatocytes. To determine the critical regulators of TLR3 signaling in response to HCV infection in human hepatocytes, we isolated endolysosome fractions from mock-infected and HCV-infected hepatoma Huh7.5 cells that had been reconstituted for TLR3 expression, separated these fractions on two-dimensional gels, and identified up-regulated/down-regulated proteins by mass spectrometry. Approximately a dozen of cellular proteins were found to be differentially expressed in endolysosome fractions following HCV infection. Of these, expression of several molecular chaperone proteins was elevated. Knockdown of one of these chaperones, glucose-regulated protein 78 kDa (GRP78), compromised TLR3-dependent induction of interferon-stimulated genes and chemokines following HCV infection or poly(I:C) stimulation in cultured hepatocytes. Consistent with this finding, GRP78 depletion impaired TLR3-mediated establishment of an antiviral state. Mechanistically, although TLR3 trafficking to endolysosomes was not affected, phosphorylated IRF3 diminished faster following GRP78 knockdown. Remarkably, GRP78 transcript was significantly up-regulated in liver biopsies of chronic hepatitis C patients as compared with normal liver tissues. Moreover, the GRP78 expression level correlated with that of RANTES (regulated upon activation, normal T-cell expressed and secreted) and CXCL10, two inflammatory chemokines most frequently elevated in HCV-infected liver. Altogether, our data suggest that GRP78 contributes to TLR3-mediated, IRF3-dependent innate immune response to HCV in hepatocytes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.