ArticleProceedings of the National Academy of Sciences of the United States of America2007
Evidence for a functional RNA element in the hepatitis C virus core gene.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
73 citing papers in PubMed, 128 citations in OpenAlex.
- Nanozymes for Liver Disease Therapy: Advances in Catalytic Activity, Targeting Strategies, and Clinical Translation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Comprehensive survey of conserved RNA secondary structures in full-genome alignment of Hepatitis C virus.Scientific reports · 2024Article
- A Proteomic Approach to Study the Biological Role of Hepatitis C Virus Protein Core+1/ARFP.Viruses · 2022Article
- TheJournal of virology · 2022Article
- Hepatitis C Viral Replication Complex.Viruses · 2021Review
- The global and local distribution of RNA structure throughout the SARS-CoV-2 genome.Journal of virology · 2021Article
- Impact of virus subtype and hostRNA (New York, N.Y.) · 2020Article
- Article
- Genotypic Regulation of Type I Interferon Induction Pathways by Frameshift (F) Proteins of Hepatitis C Virus.Journal of virology · 2020Article
- Comprehensive in-vivo secondary structure of the SARS-CoV-2 genome reveals novel regulatory motifs and mechanisms.bioRxiv : the preprint server for biology · 2020Article
- Hepatitis C Virus Translation Regulation.International journal of molecular sciences · 2020Review
- Hepatitis C Virus Replication.Cold Spring Harbor perspectives in medicine · 2020Review
- Sam68 Promotes Hepatitis C Virus Replication by Interaction with Stem-Loop 2 of Viral 5' Untranslated Region.Journal of virology · 2019Article
- Potential of the Other Genetic Information Coded by the Viral RNA Genomes as Antiviral Target.Pharmaceuticals (Basel, Switzerland) · 2019Review
- Mutational Analysis of the Bovine Hepacivirus Internal Ribosome Entry Site.Journal of virology · 2018Article
- Emergency Services of Viral RNAs: Repair and Remodeling.Microbiology and molecular biology reviews : MMBR · 2018Review
- Hepatitis C Virus core+1/ARF Protein Modulates the Cyclin D1/pRb Pathway and Promotes Carcinogenesis.Journal of virology · 2018Article
- Genetic Analysis of Serum-Derived Defective Hepatitis C Virus Genomes Revealed Novel ViralJournal of virology · 2018Article
- Signals Involved in Regulation of Hepatitis C Virus RNA Genome Translation and Replication.Frontiers in microbiology · 2018Review
- Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
In the core protein-coding region of hepatitis C virus (HCV), evidence exists for both phylogenetically conserved RNA structures and a +1 alternative reading frame (ARF). To investigate its role in HCV infection, we introduced four stop codons into the ARF of a genotype 1a H77 molecular clone. The changes did not alter the core protein sequence, but were predicted to disrupt RNA secondary structures. An attenuated infection was established after inoculation of the mutant HCV RNA into an HCV naïve chimpanzee. The acute infection was atypical with low peak viremia, minimal alanine aminotransferase elevation, and early virus control by a diverse adaptive immune response. Sequencing circulating virus revealed progressive reversions at the third and then fourth stop codon. In cell culture, RNA replication of a genome with four stop codons was severely impaired. In contrast, the revertant genome exhibited only a 5-fold reduction in replication. Genomes harboring only the first two stop codons replicated to WT levels. Similarly, reversions at stop codons 3 and 4, which improved replication, were selected with recombinant, infectious HCV in cell culture. We conclude that ARF-encoded proteins initiating at the polyprotein AUG are not essential for HCV replication in cell culture or in vivo. Rather, our results provide evidence for a functionally important RNA element in the ARF region.
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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.