title: Variation of hepatitis C virus following serial transmission: multiple mechanisms of diversification of the hypervariable region and evidence for convergent genome evolution.
abstract: We have studied the evolution of hepatitis C virus (HCV) from a common source following serial transmission from contaminated batches of anti-D immunoglobulin. Six secondary recipients were each infected with virus from identifiable primary recipients of HCV-contaminated anti-D immunoglobulin. Phylogenetic analysis of virus E1/E2 gene sequences [including the hypervariable region (HVR)] and part of NS5B confirmed their common origin, but failed to reproduce the known epidemiological relationships between pairs of viruses, probably because of the frequent occurrence of convergent substitutions at both synonymous and nonsynonymous sites. There was no evidence that the rate at which the HCV genome evolves is affected by transmission events. Three different mechanisms appear to have been involved in generating variation of the hypervariable region; nucleotide substitution, insertion/deletion of nucleotide triplets at the E1/E2 boundary and insertion of a duplicated segment replacing almost the entire HVR. These observations have important implications for the phylogenetic analysis of HCV sequences from epidemiologically linked isolates.
authors: C
authors: C
authors: Casino
authors: J
authors: J
authors: McAllister
authors: F
authors: F
authors: Davidson
authors: J
authors: J
authors: Power
authors: E
authors: E
authors: Lawlor
authors: P L
authors: PL
authors: Yap
authors: P
authors: P
authors: Simmonds
authors: D B
authors: DB
authors: Smith
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D001803:Blood Transfusion; D002648:Child; D004340:Drug Contamination; D019143:Evolution, Molecular; D005260:Female; D014644:Genetic Variation; D016679:Genome, Viral; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000453:epidemiology / Q000635:transmission* / Q000821:virology; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D007494:Ireland / Q000453:epidemiology; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010802:Phylogeny; D012189:Retrospective Studies; D018029:Rho(D) Immune Globulin / Q000008:administration & dosage; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics
chemical_list: C087035:E1 protein, Hepatitis C virus; D018029:Rho(D) Immune Globulin; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus