ArticleProceedings of the National Academy of Sciences of the United States of America2021
miR-122-based therapies select for three distinct resistance mechanisms based on alterations in RNA structure.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- DNA Framework Nucleator-Enabled Intelligent Hydrogel Interfaces on Living Cells.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Evolutionary refinement of the ZIKV 5' UTR dictates a trade-off between RNA stability and promoter accessibility.NAR molecular medicine · 2026Article
- Beyond the niche - unlocking the full potential of synthetic riboswitches.Nature communications · 2025Review
- Structural and functional characterization of the SLA' structure at the 3' terminus of the Zika virus negative-strand intermediate.RNA (New York, N.Y.) · 2025Article
- Adapted hepatitis C virus clone infects innate immunity-deficient mouse hepatocytes with minimal human HCV entry factors.JHEP reports : innovation in hepatology · 2025Article
- Extrahepatic and Circulating miR-122: Diagnostic Implications and Future Directions.MicroRNA (Shariqah, United Arab Emirates) · 2025Review
- Characterization of the SARS-CoV-2 Genome 3'-Untranslated Region Interactions with Host MicroRNAs.ACS omega · 2024Article
- Article
- Unraveling the dynamics of hepatitis C virus adaptive mutations and their impact on antiviral responses in primary human hepatocytes.Journal of virology · 2024Article
- Virus-derived circular RNAs populate hepatitis C virus-infected cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The myriad roles of RNA structure in the flavivirus life cycle.RNA biology · 2024Review
- Elucidating the distinct contributions of miR-122 in the HCV life cycle reveals insights into virion assembly.Nucleic acids research · 2023Article
- Subversion of a protein-microRNA signaling pathway by hepatitis C virus.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The Role of MicroRNAs in Liver Functioning: from Biogenesis to Therapeutic Approaches (Review).Sovremennye tekhnologii v meditsine · 2023Review
- MicroRNA-122 Regulation of HCV Infections: Insights from Studies of miR-122-Independent Replication.Pathogens (Basel, Switzerland) · 2022Review
- Review
- MicroRNA 122 Affects both the Initiation and the Maintenance of Hepatitis C Virus Infections.Journal of virology · 2022Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Hepatitis C virus (HCV) is a positive-sense RNA virus that interacts with a liver-specific microRNA called miR-122. miR-122 binds to two sites in the 5' untranslated region of the viral genome and promotes HCV RNA accumulation. This interaction is important for viral RNA accumulation in cell culture, and miR-122 inhibitors have been shown to be effective at reducing viral titers in chronic HCV-infected patients. Herein, we analyzed resistance-associated variants that were isolated in cell culture or from patients who underwent miR-122 inhibitor-based therapy and discovered three distinct resistance mechanisms all based on changes to the structure of the viral RNA. Specifically, resistance-associated variants promoted riboswitch activity, genome stability, or positive-strand viral RNA synthesis, all in the absence of miR-122. Taken together, these findings provide insight into the mechanism(s) of miR-122-mediated viral RNA accumulation and provide mechanisms of antiviral resistance mediated by changes in RNA structure.
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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.