title: Evolutionary dynamics of the E1-E2 viral populations during combination therapy in non-responder patients chronically infected with hepatitis C virus subtype 1b.
abstract: Half of the patients chronically infected with hepatitis C virus (HCV) genotype 1 fail to respond to pegylated interferon alpha (PEG-IFN) and ribavirin (RBV) therapy. This study assesses the effects of treatment on the evolution of the E1-E2 viral region in non-responder patients infected with HCV-1b. Twenty-three HCV-1b chronically infected patients were studied retrospectively, including 19 non-responders to PEG-IFN/RBV therapy (11 null-responders and 8 relapsers) in the study group, and 4 untreated patients in the control group. Genetic and phylogenetic analyses of the E1-E2 viral populations were performed at baseline and at the time of treatment failure to assess changes in genetic variability and evolutionary dynamics during treatment. Baseline virological characteristics were similar in null-responders, relapsers and controls. E1-E2 genetic variability decreased during treatment in non-responders, with a more pronounced decline in relapsers than in null-responders. A specific evolutionary pattern was not observed in null-responders, while a complete substitution of viral variants found at baseline characterised relapser patients. No specific E1-E2 amino acid substitution involved in treatment failure could be identified. In conclusion, although diverse evolutionary patterns with no apparent common adaptive changes were observed during therapy, treatment failure was characterised by a decline in genetic diversity.
authors.affiliation: Microbiology Service, Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: Saludes
authors.forename: Fernando
authors.initials: F
authors.lastname: González-Candelas
authors.forename: Ramón
authors.initials: R
authors.lastname: Planas
authors.forename: Ricard
authors.initials: R
authors.lastname: Solà
authors.forename: Vicente
authors.initials: V
authors.lastname: Ausina
authors.forename: Elisa
authors.initials: E
authors.lastname: Martró
mesh_terms: D000220:Adaptation, Biological; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D019143:Evolution, Molecular; D005260:Female; D014644:Genetic Variation; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010802:Phylogeny; D012189:Retrospective Studies; D017211:Treatment Failure; D014759:Viral Envelope Proteins / Q000235:genetics*; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; C087035:E1 protein, Hepatitis C virus; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus