ArticlePLoS pathogens2017
miRNA independent hepacivirus variants suggest a strong evolutionary pressure to maintain miR-122 dependence.
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 23 papers.
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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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Who cites it
23 citing papers in PubMed, 41 citations in OpenAlex.
- Identification of claudin-3 as an entry factor for rat hepacivirus.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The RNA Interference Effector Protein Argonaute 2 Functions as a Restriction Factor Against SARS-CoV-2.Journal of molecular biology · 2023Article
- Enhanced Virus Translation Enables miR-122-Independent Hepatitis C Virus Propagation.Journal of virology · 2023Article
- Dose-Dependent Hepacivirus Infection Reveals Linkage between Infectious Dose and Immune Response.Microbiology spectrum · 2022Article
- Equine Hepacivirus: A Systematic Review and a Meta-Analysis of Serological and Biomolecular Prevalence and a Phylogenetic Update.Animals : an open access journal from MDPI · 2022Review
- MicroRNA-122 Regulation of HCV Infections: Insights from Studies of miR-122-Independent Replication.Pathogens (Basel, Switzerland) · 2022Review
- Intra-host analysis of hepaciviral glycoprotein evolution reveals signatures associated with viral persistence and clearance.Virus evolution · 2022Article
- In the era of rapid mRNA-based vaccines: Why is there no effective hepatitis C virus vaccine yet?World journal of hepatology · 2021Review
- Pathogenesis, MicroRNA-122 Gene-Regulation, and Protective Immune Responses After Acute Equine Hepacivirus Infection.Hepatology (Baltimore, Md.) · 2021Article
- Viral Causality of Human Cancer and Potential Roles of Human Endogenous Retroviruses in the Multi-Omics Era: An Evolutionary Epidemiology Review.Frontiers in oncology · 2021Review
- The Role of the Liver-Specific microRNA, miRNA-122 in the HCV Replication Cycle.International journal of molecular sciences · 2020Review
- Evolutionary selection of pestivirus variants with altered or no microRNA dependency.Nucleic acids research · 2020Article
- Animal Models of Hepatitis C Virus Infection.Cold Spring Harbor perspectives in medicine · 2020Review
- Structure-function analysis of the equine hepacivirus 5' untranslated region highlights the conservation of translational mechanisms across the hepaciviruses.The Journal of general virology · 2019Article
- TNRC6 proteins modulate hepatitis C virus replication by spatially regulating the binding of miR-122/Ago2 complexes to viral RNA.Nucleic acids research · 2019Article
- Evolutionary biology of human hepatitis viruses.Journal of hepatology · 2019Review
- Functional Interplay between RNA Viruses and Non-Coding RNA in Mammals.Non-coding RNA · 2019Review
- miR-122, small RNA annealing and sequence mutations alter the predicted structure of the Hepatitis C virus 5' UTR RNA to stabilize and promote viral RNA accumulation.Nucleic acids research · 2018Article
- Correction: miRNA independent hepacivirus variants suggest a strong evolutionary pressure to maintain miR-122 dependence.PLoS pathogens · 2018Article
- Review
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 6 institutions in 3 countries.
Funding
Abstract
Hepatitis C virus (HCV) requires the liver specific micro-RNA (miRNA), miR-122, to replicate. This was considered unique among RNA viruses until recent discoveries of HCV-related hepaciviruses prompting the question of a more general miR-122 dependence. Among hepaciviruses, the closest known HCV relative is the equine non-primate hepacivirus (NPHV). Here, we used Argonaute cross-linking immunoprecipitation (AGO-CLIP) to confirm AGO binding to the single predicted miR-122 site in the NPHV 5'UTR in vivo. To study miR-122 requirements in the absence of NPHV-permissive cell culture systems, we generated infectious NPHV/HCV chimeric viruses with the 5' end of NPHV replacing orthologous HCV sequences. These chimeras were viable even in cells lacking miR-122, although miR-122 presence enhanced virus production. No other miRNAs bound this region. By random mutagenesis, we isolated HCV variants partially dependent on miR-122 as well as robustly replicating NPHV/HCV variants completely independent of any miRNAs. These miRNA independent variants even replicate and produce infectious particles in non-hepatic cells after exogenous delivery of apolipoprotein E (ApoE). Our findings suggest that miR-122 independent HCV and NPHV variants have arisen and been sampled during evolution, yet miR-122 dependence has prevailed. We propose that hepaciviruses may use this mechanism to guarantee liver tropism and exploit the tolerogenic liver environment to avoid clearance and promote chronicity.
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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.