ArticleJournal of virology2004
Hepatitis C virus quasispecies variability modulates nonstructural protein 5A transcriptional activation, pointing to cellular compartmentalization of virus-host interactions.
Article in Journal of virology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Article
- Vector-Transmitted Flaviviruses: An Antiviral Molecules Overview.Microorganisms · 2023Review
- Genome-Wide Mutagenesis of Hepatitis C Virus Reveals Ability of Genome To Overcome Detrimental Mutations.Journal of virology · 2020Article
- Efficacy of a 3C-like protease inhibitor in treating various forms of acquired feline infectious peritonitis.Journal of feline medicine and surgery · 2018Article
- Hepatitis C virus genetic variability and evolution.World journal of hepatology · 2015Review
- Hepatitis C virus molecular evolution: transmission, disease progression and antiviral therapy.World journal of gastroenterology · 2014Review
- Evidence of distinct populations of hepatitis C virus in the liver and plasma of patients co-infected with HIV and HCV.Journal of medical virology · 2014Article
- Regulation of hepatitis C virus replication by nuclear translocation of nonstructural 5A protein and transcriptional activation of host genes.Journal of virology · 2013Article
- Analysis of HCV quasispecies dynamic under selective pressure of combined therapy.BMC infectious diseases · 2013Article
- Analysis of a non-structural gene reveals evidence of possible hepatitis C virus (HCV) compartmentalization.Journal of medical virology · 2012Article
- Mechanism of resistance of hepatitis C virus replicons to structurally distinct cyclophilin inhibitors.Antimicrobial agents and chemotherapy · 2010Article
- The quasispecies nature and biological implications of the hepatitis C virus.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2009Review
- Article
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatitis C virus (HCV) behaves in infected patients as a complex mixture of genetically distinct but closely related variants referred to as a "quasispecies." By using quasispecies analysis strategies, we showed that HCV nonstructural protein 5A (NS5A) has a quasispecies distribution in infected humans and that NS5A quasispecies undergo significant genetic evolution over time, as a result of random accumulation of nucleotide mutations during replication. Genetic evolution of the NS5A quasispecies results in sporadic amino acid changes in the protein sequence. By using the functional in vitro model of HCV NS5A transcriptional activation in Saccharomyces cerevisiae, we showed that natural NS5A quasispecies variants induce different levels of transcriptional activation, according to the charge of the residues (and possibly minor conformational changes) in the quasispecies variant sequence. These findings show that the accumulation of mutations on HCV genomes during replication randomly generates variant proteins with quantitatively different functional properties. The fact that each new variant protein is initially produced in a single infected hepatocyte and may or may not subsequently spread throughout the liver (depending on the replication capacities of the variant virus) points to cellular compartmentalization of virus-host interactions during chronic infection. This feature of quasispecies-distributed viruses could play an important role in various aspects of the viral life cycle and related disease.
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