ArticleHepatology (Baltimore, Md.)2015
Novel perspectives for hepatitis A virus therapy revealed by comparative analysis of hepatitis C virus and hepatitis A virus RNA replication.
Article in Hepatology (Baltimore, Md.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
24 citing papers in PubMed, 42 citations in OpenAlex.
- Azathioprine Inhibits Hepatitis A Virus Replication In Vitro.Pathogens (Basel, Switzerland) · 2026Article
- Zinc Acetate Inhibits Hepatitis A Virus Replication: Possible Treatment for Patients with Type A Acute-on-Chronic Liver Failure.Pathogens (Basel, Switzerland) · 2025Article
- Reconstitution of interferon regulatory factor 7 expression restores interferon beta induction in Huh7 cells.Journal of virology · 2025Article
- Limited impact of hepatitis A virus 3C protease-mediated cleavage on the functions of NEMO in human hepatocytes.Journal of virology · 2025Article
- Potential role of microRNAs in personalized medicine against hepatitis: a futuristic approach.Archives of virology · 2024Review
- The hepatitis E virus ORF1 hypervariable region confers partial cyclophilin dependency.The Journal of general virology · 2023Article
- Masitinib Inhibits Hepatitis A Virus Replication.International journal of molecular sciences · 2023Article
- Viral protease cleavage of MAVS in genetically modified mice with hepatitis A virus infection.Journal of hepatology · 2023Article
- Hepatitis A: Viral Structure, Classification, Life Cycle, Clinical Symptoms, Diagnosis Error, and Vaccination.The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2023Review
- Macrophage Depletion Reactivates Fecal Virus Shedding following Resolution of Acute Hepatitis A inJournal of virology · 2022Article
- High-Order Epistasis and Functional Coupling of Infection Steps Drive Virus Evolution toward Independence from a Host Pathway.Microbiology spectrum · 2021Article
- Picornaviruses: A View from 3A.Viruses · 2021Review
- Co-Occurrence of Hepatitis A Infection and Chronic Liver Disease.International journal of molecular sciences · 2020Review
- Convergent evolution in the mechanisms of ACBD3 recruitment to picornavirus replication sites.PLoS pathogens · 2019Article
- Hepatitis A Virus Genome Organization and Replication Strategy.Cold Spring Harbor perspectives in medicine · 2018Review
- Viral rewiring of cellular lipid metabolism to create membranous replication compartments.Current opinion in cell biology · 2017Review
- The role of nanotechnology in the treatment of viral infections.Therapeutic advances in infectious disease · 2017Review
- Interaction and Mutual Activation of Different Innate Immune Cells Is Necessary to Kill and Clear Hepatitis C Virus-Infected Cells.Frontiers in immunology · 2017Article
- Foot-and-mouth disease virus replicates independently of phosphatidylinositol 4-phosphate and type III phosphatidylinositol 4-kinases.The Journal of general virology · 2016Article
- The cyclophilin-inhibitor alisporivir stimulates antigen presentation thereby promoting antigen-specific CD8(+) T cell activation.Journal of hepatology · 2016Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
unlabelledHepatitis A virus (HAV) and hepatitis C virus (HCV) are two positive-strand RNA viruses sharing a similar biology, but causing opposing infection outcomes, with HAV always being cleared and HCV establishing persistence in the majority of infections. To gain deeper insight into determinants of replication, persistence, and treatment, we established a homogenous cell-culture model allowing a thorough comparison of RNA replication of both viruses. By screening different human liver-derived cell lines with subgenomic reporter replicons of HAV as well as of different HCV genotypes, we found that Huh7-Lunet cells supported HAV- and HCV-RNA replication with similar efficiency and limited interference between both replicases. HAV and HCV replicons were similarly sensitive to interferon (IFN), but differed in their ability to establish persistent replication in cell culture. In contrast to HCV, HAV replicated independently from microRNA-122 and phosphatidylinositol 4-kinase IIIα and β (PI4KIII). Both viruses were efficiently inhibited by cyclosporin A and NIM811, a nonimmunosuppressive analog thereof, suggesting an overlapping dependency on cyclophilins for replication. However, analysis of a broader set of inhibitors revealed that, in contrast to HCV, HAV does not depend on cyclophilin A, but rather on adenosine-triphosphate-binding cassette transporters and FK506-binding proteins. Finally, silibinin, but not its modified intravenous formulation, efficiently inhibited HAV genome replication in vitro, suggesting oral silibinin as a potential therapeutic option for HAV infections.
conclusionWe established a cell-culture model enabling comparative studies on RNA replication of HAV and HCV in a homogenous cellular background with comparable replication efficiency. We thereby identified new host cell targets and potential treatment options for HAV and set the ground for future studies to unravel determinants of clearance and persistence.
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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.