ArticleNature communications2021
Viral genome wide association study identifies novel hepatitis C virus polymorphisms associated with sofosbuvir treatment failure.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 22 citations in OpenAlex.
- A G-Quadruplex-Activated Near-Infrared Chemiluminescent Probe for In Situ Hepatic Imaging of the Hepatitis C Virus Genome.Angewandte Chemie (International ed. in English) · 2026Article
- Interplay of host and viral genetic variations in modulating antibody responses to genotype 3a hepatitis C virus: Implications for vaccine design.Cell reports · 2025Article
- Genetically distinct within-host subpopulations of hepatitis C virus persist after Direct-Acting Antiviral treatment failure.PLoS pathogens · 2025Article
- Article
- Viral Genomic Variation and the Severity of Genital Herpes Simplex Virus-2 Infection as Quantified by Shedding Rate: A Viral Genome-Wide Association Study.The Journal of infectious diseases · 2024Article
- Single-molecule sequencing of the whole HCV genome revealed envelope deletions in decompensated cirrhosis associated with NS2 and NS5A mutations.Journal of gastroenterology · 2024Article
- Rare HCV subtypes and retreatment outcomes in a cohort of European DAA-experienced patients.JHEP reports : innovation in hepatology · 2024Article
- Epidemiology of Hepatitis C Virus in HIV Patients from West Mexico: Implications for Controlling and Preventing Viral Hepatitis.Pathogens (Basel, Switzerland) · 2024Article
- Intergenomic signatures of coevolution between Tasmanian devils and an infectious cancer.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Full-length sequence analysis of hepatitis C virus genotype 3b strains and development of anJournal of virology · 2023Article
- Article
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Authors and funding
16 authors at 20 institutions in 8 countries.
Funding
Abstract
Persistent hepatitis C virus (HCV) infection is a major cause of chronic liver disease, worldwide. With the development of direct-acting antivirals, treatment of chronically infected patients has become highly effective, although a subset of patients responds less well to therapy. Sofosbuvir is a common component of current de novo or salvage combination therapies, that targets the HCV NS5B polymerase. We use pre-treatment whole-genome sequences of HCV from 507 patients infected with HCV subtype 3a and treated with sofosbuvir containing regimens to detect viral polymorphisms associated with response to treatment. We find three common polymorphisms in non-targeted HCV NS2 and NS3 proteins are associated with reduced treatment response. These polymorphisms are enriched in post-treatment HCV sequences of patients unresponsive to treatment. They are also associated with lower reductions in viral load in the first week of therapy. Using in vitro short-term dose-response assays, these polymorphisms do not cause any reduction in sofosbuvir potency, suggesting an indirect mechanism of action in decreasing sofosbuvir efficacy. The identification of polymorphisms in NS2 and NS3 proteins associated with poor treatment outcomes emphasises the value of systematic genome-wide analyses of viruses in uncovering clinically relevant polymorphisms that impact treatment.
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