Hepatitis C virus (HCV) shows remarkable genetic variationin 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.
Sequence variation in the hypervariable Region 1 of hepatitis C virus and posttransplantation recurrent hepatitis
Lisa A;
2003
Abstract
Hepatitis C virus (HCV) shows remarkable genetic variationin 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
