ArticleProceedings of the National Academy of Sciences of the United States of America2011
MicroRNA-122 antagonism against hepatitis C virus genotypes 1-6 and reduced efficacy by host RNA insertion or mutations in the HCV 5' UTR.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
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Who cites it
101 citing papers in PubMed, 184 citations in OpenAlex.
- Immune phenotype and function of natural killer and T cells in chronic hepatitis C patients who received a single dose of anti-MicroRNA-122, RG-101.Hepatology (Baltimore, Md.) · 2017Trial
- In vitro antiviral activity and preclinical and clinical resistance profile of miravirsen, a novel anti-hepatitis C virus therapeutic targeting the human factor miR-122.Antimicrobial agents and chemotherapy · 2015Trial
- Reducing haystacks to needles-ViralClust: a Nextflow pipeline to cluster viral sequences.GigaScience · 2026Article
- Review
- Full-length sequence analysis of hepatitis C virus genotype 3b strains and development of anJournal of virology · 2023Article
- ATAD1 inhibits hepatitis C virus infection by removing the viral TA-protein NS5B from mitochondria.EMBO reports · 2023Article
- Enhanced Virus Translation Enables miR-122-Independent Hepatitis C Virus Propagation.Journal of virology · 2023Article
- Article
- Hepatitis C virus hypervariable region 1 antibodies interrupt E2-SR-B1 interaction to suppress viral infection.iScience · 2023Article
- Novel HCV Genotype 4d Infectious Systems and Assessment of Direct-Acting Antivirals and Antibody Neutralization.Viruses · 2022Article
- MicroRNA-122 Regulation of HCV Infections: Insights from Studies of miR-122-Independent Replication.Pathogens (Basel, Switzerland) · 2022Review
- PPP2R5D promotes hepatitis C virus infection by binding to viral NS5B and enhancing viral RNA replication.Virology journal · 2022Article
- MicroRNA 122 Affects both the Initiation and the Maintenance of Hepatitis C Virus Infections.Journal of virology · 2022Article
- Noncoding RNA therapeutics - challenges and potential solutions.Nature reviews. Drug discovery · 2021Review
- Overcoming Culture Restriction for SARS-CoV-2 in Human Cells Facilitates the Screening of Compounds Inhibiting Viral Replication.Antimicrobial agents and chemotherapy · 2021Article
- From Structural Studies to HCV Vaccine Design.Viruses · 2021Review
- Keyhole Limpet Hemocyanin-Conjugated Peptides from Hepatitis C Virus Glycoproteins Elicit Neutralizing Antibodies in BALB/c Mice.Journal of immunology research · 2021Article
- 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
- TNRC6 proteins modulate hepatitis C virus replication by spatially regulating the binding of miR-122/Ago2 complexes to viral RNA.Nucleic acids research · 2019Article
41 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
MicroRNA-122 (miR-122) is believed to stimulate hepatitis C virus (HCV) replication through interaction with two adjacent sites downstream of stem loop I (SLI) within the HCV 5' untranslated region (5' UTR). Recently, it was demonstrated that locked nucleic acid SPC3649-induced miR-122 antagonism suppressed HCV genotype 1a and 1b infection in vivo. However, virus-producing culture systems with 5' UTR of different HCV genotypes have not been available for testing 5' UTR-based treatment approaches. Using JFH1-based Core-NS2 genotype recombinants, we developed 5' UTR-NS2 recombinants of HCV genotypes 1a, 1b, 2a, 2b, 3a, 4a, 5a, and 6a with efficient growth in Huh7.5 cells. Deletion mutagenesis studies demonstrated that the 5' UTR SLI was essential for genotypes 1-6 infection. However, lack of SLI could be compensated for by insertion of other structured HCV or host RNA sequences, including U3 small nucleolar RNA. We demonstrated that SPC3649-induced miR-122 antagonism had a potent antiviral effect against HCV genotypes 1-6 5' UTR-NS2 viruses. Strikingly, HCV recombinant virus with substitution of SLI and miR-122 binding site 1 (S1) by the U3 RNA sequence was not affected by miR-122 antagonism; this was attributed to the lack of an intact S1 by reverse genetics studies. Therefore, we engineered the corresponding U3 RNA sequences into S1 and demonstrated that HCV recombinants with wild-type SLI and single or combined mutations at four of eight nucleotides of S1 were viable in Huh7.5 cells. These mutations reduced the efficacy of SPC3649 treatment, indicating that escape variants to miR-122 antagonism-based HCV therapy could potentially occur.
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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.