title: Evolutionary trends of the first hypervariable region of the hepatitis C virus E2 protein in individuals with differing liver disease severity.
abstract: Hepatitis C virus (HCV) exists as a complex swarm of genetically related viruses known as a quasispecies. Recent work has shown that quasispecies complexity and evolutionary rates are associated with the outcome of acute infection. Knowledge of how the virus population evolves at different stages of chronic infection is less clear. We have studied rates of evolution of the first hypervariable region (HVR1) of the E2 envelope protein in six individuals with disparate liver disease severity. These data show that virus populations present in individuals with mild non-progressive liver disease evolve in a typical Darwinian fashion, with a consistent accumulation of non-synonymous (amino acid-changing) substitutions. By contrast, the virus population remains relatively static in individuals with severe progressive liver disease. Possible mechanisms for this disparity are discussed.
authors.affiliation: Division of Microbiology and Infectious Diseases, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK1.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Curran
authors.affiliation: Division of Microbiology and Infectious Diseases, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK1.
authors.forename: Claire L
authors.initials: CL
authors.lastname: Jameson
authors.affiliation: Division of Microbiology and Infectious Diseases, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK1.
authors.forename: Joanna K
authors.initials: JK
authors.lastname: Craggs
authors.affiliation: Division of Microbiology and Infectious Diseases, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK1.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Grabowska
authors.affiliation: Division of Microbiology and Infectious Diseases, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK1.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Thomson
authors.affiliation: Division of Microbiology and Infectious Diseases, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK1.
authors.forename: Adrian
authors.initials: A
authors.lastname: Robins
authors.affiliation: Division of Microbiology and Infectious Diseases, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK1.
authors.forename: William L
authors.initials: WL
authors.lastname: Irving
authors.affiliation: Division of Microbiology and Infectious Diseases, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK1.
authors.forename: Jonathan K
authors.initials: JK
authors.lastname: Ball
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000596:Amino Acids; D001483:Base Sequence; D001665:Binding Sites; D019143:Evolution, Molecular; D014644:Genetic Variation; D016174:Hepacivirus / Q000145:classification / Q000235:genetics*; D006526:Hepatitis C / Q000378:metabolism / Q000503:physiopathology* / Q000821:virology; D018936:Hepatitis C Antigens / Q000145:classification / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000378:metabolism / Q000503:physiopathology / Q000821:virology; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000503:physiopathology / Q000821:virology; D008107:Liver Diseases / Q000378:metabolism / Q000503:physiopathology / Q000821:virology; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009711:Nucleotides; D010802:Phylogeny; D021382:Protein Sorting Signals; D017422:Sequence Analysis, DNA; D014759:Viral Envelope Proteins / Q000145:classification / Q000235:genetics*; D019562:Viral Load
chemical_list: D000596:Amino Acids; D018936:Hepatitis C Antigens; D009711:Nucleotides; D021382:Protein Sorting Signals; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus; D000410:Alanine Transaminase