ArticleVirology journal2012
Free fatty acids induce ER stress and block antiviral activity of interferon alpha against hepatitis C virus in cell culture.
Article in Virology journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 48 citations in OpenAlex.
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- Sex differences in murine MASH induced by a fructose-palmitate-cholesterol-enriched diet.JHEP reports : innovation in hepatology · 2025Article
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- Subtilase cytotoxin from Shiga-toxigeniciScience · 2022Article
- Interactions of Autophagy and the Immune System in Health and Diseases.Autophagy reports · 2022Article
- The Impact of Steatosis on Chronic Hepatitis C Progression and Response to Antiviral Treatments.Biomedicines · 2021Review
- Antiviral screening onHeliyon · 2021Article
- Correlation between bioactive lipids and novel coronavirus: constructive role of biolipids in curbing infectivity by enveloped viruses, centralizing on EPA and DHA.Systems microbiology and biomanufacturing · 2021Review
- A Review of Current Interventions for COVID-19 Prevention.Archives of medical research · 2020Review
- Integrated stress response in hepatitis C promotes Nrf2-related chaperone-mediated autophagy: A novel mechanism for host-microbe survival and HCC development in liver cirrhosis.Seminars in cell & developmental biology · 2020Review
- Mechanism and Complex Roles of HSC70 in Viral Infections.Frontiers in microbiology · 2020Review
- Palmitic Acid Promotes Virus Replication in Fish Cell by Modulating Autophagy Flux and TBK1-IRF3/7 Pathway.Frontiers in immunology · 2020Article
- Type I interferons and endoplasmic reticulum stress in health and disease.International review of cell and molecular biology · 2020Review
- Review
- Crosstalk between Autophagy and Type I Interferon Responses in Innate Antiviral Immunity.Viruses · 2019Review
- High intensity focused electromagnetic therapy evaluated by magnetic resonance imaging: Safety and efficacy study of a dual tissue effect based non-invasive abdominal body shaping.Lasers in surgery and medicine · 2019Article
- Janus Kinase 1 Is Required for Transcriptional Reprograming of Murine Astrocytes in Response to Endoplasmic Reticulum Stress.Frontiers in cellular neuroscience · 2019Article
- Serum Lipidomics Analysis of Classical Swine Fever Virus Infection in Piglets and Emerging Role of Free Fatty Acids in Virus ReplicationFrontiers in cellular and infection microbiology · 2019Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundHepatic steatosis is recognized as a major risk factor for liver disease progression and impaired response to interferon based therapy in chronic hepatitis C (CHC) patients. The mechanism of response to interferon-alpha (IFN-α) therapy under the condition of hepatic steatosis is unexplored. We investigated the effect of hepatocellular steatosis on hepatitis C virus (HCV) replication and IFN-α antiviral response in a cell culture model.
methodsSub-genomic replicon (S3-GFP) and HCV infected Huh-7.5 cells were cultured with a mixture of saturated (palmitate) and unsaturated (oleate) long-chain free fatty acids (FFA). Intracytoplasmic fat accumulation in these cells was visualized by Nile red staining and electron microscopy then quantified by microfluorometry. The effect of FFA treatment on HCV replication and IFN-α antiviral response was measured by flow cytometric analysis, Renilla luciferase activity, and real-time RT-PCR.
resultsFFA treatment induced dose dependent hepatocellular steatosis and lipid droplet accumulation in the HCV replicon cells was confirmed by Nile red staining, microfluorometry, and by electron microscopy. Intracellular fat accumulation supports replication more in the persistently HCV infected culture than in the sub-genomic replicon (S3-GFP) cell line. FFA treatment also partially blocked IFN-α response and viral clearance by reducing the phosphorylation of Stat1 and Stat2 dependent IFN-β promoter activation. We show that FFA treatment induces endoplasmic reticulum (ER) stress response and down regulates the IFNAR1 chain of the type I IFN receptor leading to defective Jak-Stat signaling and impaired antiviral response.
conclusionThese results suggest that intracellular fat accumulation in HCV cell culture induces ER stress, defective Jak-Stat signaling, and attenuates the antiviral response, thus providing an explanation to the clinical observation regarding how hepatocellular steatosis influences IFN-α response in CHC.
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