ArticleGastroenterology2011
Protease inhibitor-resistant hepatitis C virus mutants with reduced fitness from impaired production of infectious virus.
Article in Gastroenterology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 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.
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Who cites it
80 citing papers in PubMed, 132 citations in OpenAlex.
- The paradox of highly effective sofosbuvir-based combination therapy despite slow viral decline: can we still rely on viral kinetics?Scientific reports · 2017Trial
- Safety and efficacy of dual therapy with daclatasvir and asunaprevir for older patients with chronic hepatitis C.Journal of gastroenterology · 2017Trial
- Virological response and safety of 24-week telaprevir alone in Japanese patients infected with hepatitis C virus subtype 1b.Journal of viral hepatitis · 2013Trial
- Novel Pyrazino[1,2-Viruses · 2024Article
- A single hepatitis B virus genome with a reporter allows the entire viral life cycle to be monitored in primary human hepatocytes.Hepatology communications · 2022Article
- Leukocyte cell-derived chemotaxin 2 is an antiviral regulator acting through the proto-oncogene MET.Nature communications · 2022Article
- Design and Synthesis of Novel Bis-Imidazolyl Phenyl Butadiyne Derivatives as HCV NS5A Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Regulatory Role of Phospholipids in Hepatitis C Virus Replication and Protein Function.Pathogens (Basel, Switzerland) · 2022Review
- Epistatic interactions promote persistence of NS3-Q80K in HCV infection by compensating for protein folding instability.The Journal of biological chemistry · 2021Article
- Longer Poly(U) Stretches in the 3'UTR Are Essential for Replication of the Hepatitis C Virus Genotype 4a Clone inFrontiers in microbiology · 2021Article
- Extended interaction networks with HCV protease NS3-4A substrates explain the lack of adaptive capability against protease inhibitors.The Journal of biological chemistry · 2020Article
- Pre-existing resistance associated polymorphisms to NS3 protease inhibitors in treatment naïve HCV positive Pakistani patients.PloS one · 2020Article
- Cell Culture Systems of HCV Using JFH-1 and Other Strains.Cold Spring Harbor perspectives in medicine · 2019Review
- Interplay of Amino Acid Residues at Positions 28 and 31 in NS5A Defines Resistance Pathways in HCV GT2.Antimicrobial agents and chemotherapy · 2019Article
- Evolutionary Pathways to Persistence of Highly Fit and Resistant Hepatitis C Virus Protease Inhibitor Escape Variants.Hepatology (Baltimore, Md.) · 2019Review
- Near-Neighbor Interactions in the NS3-4A Protease of HCV Impact Replicative Fitness of Drug-Resistant Viral Variants.Journal of molecular biology · 2019Article
- Establishment and Characterization of a New Cell Line Permissive for Hepatitis C Virus Infection.Scientific reports · 2019Article
- Impact of a patient-derived hepatitis C viral RNA genome with a mutated microRNA binding site.PLoS pathogens · 2019Article
- Article
- Evolutionary pathways to NS5A inhibitor resistance in genotype 1 hepatitis C virus.Antiviral research · 2018Article
20 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
7 authors at 3 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsSeveral small molecule inhibitors of the hepatitis C virus (HCV) nonstructural protein (NS) 3/4A protease have advanced successfully to clinical trials. However, the selection of drug-resistant mutants is a significant issue with protease inhibitors (PIs). A variety of amino acid substitutions in the protease domain of NS3 can lead to PI resistance. Many of these significantly impair the replication fitness of HCV RNA replicons. However, it is not known whether these mutations also adversely affect infectious virus assembly and release, processes in which NS3 also participates.
methodsWe studied the impact of 25 previously identified PI-resistance mutations on the capacity of genotype 1a H77S RNA to replicate in cell culture and produce infectious virus.
resultsMost PI-resistance mutations resulted in moderate loss of replication competence, although several (V36A/L/M, R109K, and D168E) showed fitness comparable to wild type, whereas others (S138T and A156V) were severely impaired both in RNA replication and infectious virus production. Although reductions in RNA replication capacity correlated with decreased yields of infectious virus for most mutations, a subset of mutants (Q41R, F43S, R155T, A156S, and I170A/T) showed greater impairment in their ability to produce virus than predicted from reductions in RNA replication capacity. Detailed examination of the I170A mutant showed no defect in release of virus from cells and no significant difference in specific infectivity of extracellular virus particles.
conclusionsReplicon-based assays might underestimate the loss of fitness caused by PI-resistance mutations, because some mutations in the NS3 protease domain specifically impair late steps in the viral life cycle that involve intracellular assembly of infectious virus.
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What OpenQuestion holds
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.