title: Insertion and recombination events at hypervariable region 1 over 9.6 years of hepatitis C virus chronic infection.
abstract: Hepatitis C virus (HCV) exists as a quasispecies within an infected individual. We have previously reported an in-frame 3 bp insertion event at the N-terminal region of the E2 glycoprotein from a genotype 4a HCV isolate giving rise to an atypical 28 aa hypervariable region (HVR) 1. To further explore quasispecies evolution at the HVR1, serum samples collected over 9.6 years from the same chronically infected, treatment naïve individual were subjected to retrospective clonal analysis. Uniquely, we observed that isolates containing this atypical HVR1 not only persisted for 7.6 years, but dominated the quasispecies swarm. Just as striking was the collapse of this population of variants towards the end of the sampling period in synchrony with variants containing a classical HVR1 from the same lineage. The replication space was subsequently occupied by a second minor lineage, which itself was only intermittently detectable at earlier sampling points. In conjunction with the observed genetic shift, the coexistence of two distinct HVR1 populations facilitated the detection of putative intra-subtype recombinants, which included the identification of the likely ancestral parental donors. Juxtaposed to the considerable plasticity of the HVR1, we also document a degree of mutational inflexibility as each of the HVR1 subpopulations within our dataset exhibited overall genetic conservation and convergence. Finally, we raise the issue of genetic analysis in the context of mixed lineage infections.
authors.affiliation: Molecular Virology Diagnostic and Research Laboratory, Department of Medicine, Clinical Sciences Building, University College Cork, Cork, Ireland.
authors.forename: Brendan A
authors.initials: BA
authors.lastname: Palmer
authors.affiliation: Molecular Virology Diagnostic and Research Laboratory, Department of Medicine, Clinical Sciences Building, University College Cork, Cork, Ireland.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Moreau
authors.affiliation: Molecular Virology Diagnostic and Research Laboratory, Department of Medicine, Clinical Sciences Building, University College Cork, Cork, Ireland.
authors.forename: John
authors.initials: J
authors.lastname: Levis
authors.affiliation: Molecular Virology Diagnostic and Research Laboratory, Department of Medicine, Clinical Sciences Building, University College Cork, Cork, Ireland.
authors.forename: Ciara
authors.initials: C
authors.lastname: Harty
authors.affiliation: Department of Gastroenterology, Cork University Hospital, Cork, Ireland.
authors.forename: Orla
authors.initials: O
authors.lastname: Crosbie
authors.affiliation: Department of Gastroenterology, Cork University Hospital, Cork, Ireland.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Kenny-Walsh
authors.affiliation: Molecular Virology Diagnostic and Research Laboratory, Department of Medicine, Clinical Sciences Building, University College Cork, Cork, Ireland.
authors.forename: Liam J
authors.initials: LJ
authors.lastname: Fanning
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D004279:DNA, Viral / Q000235:genetics; D019143:Evolution, Molecular; D016174:Hepacivirus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000821:virology*; D006801:Humans; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D010802:Phylogeny; D011995:Recombination, Genetic; D012689:Sequence Homology, Nucleic Acid; D013997:Time Factors; D014764:Viral Proteins / Q000235:genetics*
chemical_list: D004279:DNA, Viral; C400562:HVR1 protein, Hepatitis C virus; D014764:Viral Proteins