ArticleJHEP reports : innovation in hepatology2023
Hepatitis C virus replication requires integrity of mitochondria-associated ER membranes.
Article in JHEP reports : innovation in hepatology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- Remodeling of Metabolic and Secretory Organelles During Oncogenic and Oncomodulatory Viral Infections.Viruses · 2026Review
- Review
- Mitochondria-endoplasmic reticulum contact sites in hepatocytic senescence.Cellular & molecular biology letters · 2026Review
- Online Conference "Chronic Viral Infections and Cancer, Openings for Vaccines and Cure" VIRCAN2024, Monitoring the Progress.Vaccines · 2025Article
- Metabolic Imprint of Poliovirus on Glioblastoma Cells and Its Role in Virus Replication and Cytopathic Activity.International journal of molecular sciences · 2025Article
- Review
- The Malignant Transformation of Viral Hepatitis to Hepatocellular Carcinoma: Mechanisms and Interventions.MedComm · 2025Review
- Prognostic assessment of early-stage liver cirrhosis induced by HCV using an integrated model of CX3CR1-associated immune infiltration genes.Scientific reports · 2025Article
- Article
- Viral regulation of organelle membrane contact sites.PLoS biology · 2024Article
- Review
- HCV-induced autophagy and innate immunity.Frontiers in immunology · 2024Review
- Endoplasmic reticulum stress and mitochondrial dysfunction during aging: Role of sphingolipids.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2023Article
- Host mitochondria: more than an organelle in SARS-CoV-2 infection.Frontiers in cellular and infection microbiology · 2023Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background & Aims: Chronic HCV infection causes cellular stress, fibrosis and predisposes to hepatocarcinogenesis. Mitochondria play key roles in orchestrating stress responses by regulating bioenergetics, inflammation and apoptosis. To better understand the role of mitochondria in the viral life cycle and disease progression of chronic hepatitis C, we studied morphological and functional mitochondrial alterations induced by HCV using productively infected hepatoma cells and patient livers. Methods: Biochemical and imaging assays were used to assess localization of cellular and viral proteins and mitochondrial functions in cell cultures and liver biopsies. Cyclophilin D (CypD) knockout was performed using CRISPR/Cas9 technology. Viral replication was quantified by quantitative reverse-transcription PCR and western blotting. Results: Several HCV proteins were found to associate with mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs), the points of contact between the ER and mitochondria. Downregulation of CypD, which is known to disrupt MAM integrity, reduced viral replication, suggesting that MAMs play an important role in the viral life cycle. This process was rescued by ectopic CypD expression. Furthermore, HCV proteins were found to associate with voltage dependent anion channel 1 (VDAC1) at MAMs and to reduce VDAC1 protein levels at MAMs Conclusions: HCV proteins associate specifically with MAMs and MAMs play an important role in viral replication. The association between viral proteins and MAMs did not impact Ca Impact and implications: Hepatitis C virus infects the liver, where it causes inflammation, cell damage and increases the long-term risk of liver cancer. We show that several HCV proteins interact with mitochondria in liver cells and alter the composition of mitochondrial subdomains. Importantly, HCV requires the architecture of these mitochondrial subdomains to remain intact for efficient viral replication.
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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.