title: Sequence variation in the hypervariable region 1 of hepatitis C virus and posttransplantation recurrent hepatitis.
abstract: Hepatitis C virus (HCV) shows remarkable genetic variation in both populations and individuals, in whom it circulates as quasispecies (QS). Sequence variation within an infected host has adaptive significance and reflects the modes and intensity of selection mechanisms operating on the virus. We investigated the sequence diversity of hypervariable region 1 of HCV in liver transplant recipients and correlated it with the recurrence of hepatitis. Twenty-six patients were considered during a 2-year period; all had graft reinfection, and 14 patients developed hepatitis recurrence. Cloned sequences were obtained from sera collected before or within 1 month after orthotopic liver transplantation (OLT) and at 3 and 24 months thereafter. Sequence diversity within single sera and over consecutive samples was analyzed quantitatively by matrix comparison and phylogenetic analysis. Propagation of viral QS in the graft was markedly dependent on individual factors. Viral QS in post-OLT sera were less complex and evolved slower compared with immunocompetent subjects with chronic hepatitis. Sequence variation was greater during the first 3 months post-OLT than during the remaining period. Genetic diversity within single samples was not related to hepatitis recurrence or other clinical features. Conversely, sequence diversity over consecutive samples was reduced in patients who experienced hepatitis recurrence, in particular, in those infected with genotype 1b and with an HLA-DR mismatched graft. Selection of viral sequences was markedly impaired in liver transplant recipients and tended to be greater early after OLT. Reduced sequence turnover correlated negatively with the outcome of graft reinfection.
authors.affiliation: Department of Pathology, University and IRCCS-S, Matteo, Italy. silinien@unipv.it
authors.forename: Enrico
authors.initials: E
authors.lastname: Silini
authors.forename: Luca
authors.initials: L
authors.lastname: Belli
authors.forename: Sabrina
authors.initials: S
authors.lastname: Brambilla
authors.forename: Luciana
authors.initials: L
authors.lastname: Foti
authors.forename: Chiara
authors.initials: C
authors.lastname: Gritti
authors.forename: Antonella
authors.initials: A
authors.lastname: Lisa
authors.forename: Alberto Battista
authors.initials: AB
authors.lastname: Alberti
authors.forename: Marilina
authors.initials: M
authors.lastname: Vinci
authors.forename: Luciano
authors.initials: L
authors.lastname: De Carlis
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Rondinara
authors.forename: Giovanbattista
authors.initials: G
authors.lastname: Pinzello
mesh_terms: D000328:Adult; D003001:Cloning, Molecular; D005260:Female; D016174:Hepacivirus / Q000235:genetics* / Q000254:growth & development; D019698:Hepatitis C, Chronic / Q000601:surgery* / Q000821:virology*; D006801:Humans; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D010802:Phylogeny; D011183:Postoperative Complications / Q000821:virology; D012008:Recurrence; D014764:Viral Proteins / Q000235:genetics*; D014779:Virus Replication
chemical_list: C400562:HVR1 protein, Hepatitis C virus; D014764:Viral Proteins