title: Evolution of hepatitis C virus quasispecies in renal transplant patients with de novo glomerulonephritis.
abstract: Long-term renal allograft survival in kidney transplant recipients infected by hepatitis C virus (HCV) may be influenced by the occurrence of de novo glomerulopathy associated with this virus. Therefore, we studied the evolution of HCV quasispecies in kidney transplant recipients infected by HCV with or without de novo glomerulopathy. The hypervariable region 1 (HVR-1) of the virus envelope was analyzed by cloning and sequencing 20 clones per sample to assess complexity and diversity from six kidney transplant patients who developed de novo glomerulopathy (group I) matched to six kidney transplant recipients without glomerular disease (group II), according to age, time since renal transplantation, and HCV genotype. Two sera were analyzed for each patient: one at the time of renal transplantation and the other at the time of appearance of de novo glomerulopathy, or after a similar duration since transplantation in group II. Overall, there was a significant increase of HCV viremia after the transplantation. This increase did not differ significantly between group I (+0.5 log copies/ml) and group II patients (+1 log copies/ml). The intersample diversity of HCV was similar in the two groups. Complexity and viral diversity were also similar at the time of transplantation. By contrast, complexity, diversity, and the proportion of nonsynonymous substitutions per nonsynonymous site were significantly higher after transplantation in group I patients. Our findings suggest a higher immune response and/or a particular cytokine production in patients developing de novo glomerulopathy rather than a direct effect of HCV on renal cells.
authors.affiliation: Department of Nephrology, Dialysis and Transplantation, CHU Rangueil, Toulouse Cedex, France.
authors.forename: Nassim
authors.initials: N
authors.lastname: Kamar
authors.forename: Lionel
authors.initials: L
authors.lastname: Rostaing
authors.forename: Anne
authors.initials: A
authors.lastname: Boulestin
authors.forename: Karine
authors.initials: K
authors.lastname: Sandres
authors.forename: Martine
authors.initials: M
authors.lastname: Dubois
authors.forename: David
authors.initials: D
authors.lastname: Ribes
authors.forename: Anne
authors.initials: A
authors.lastname: Modesto
authors.forename: Dominique
authors.initials: D
authors.lastname: Durand
authors.forename: Jacques
authors.initials: J
authors.lastname: Izopet
mesh_terms: D000328:Adult; D003001:Cloning, Molecular; D019143:Evolution, Molecular; D005260:Female; D014644:Genetic Variation; D005921:Glomerulonephritis / Q000150:complications / Q000821:virology*; D016174:Hepacivirus / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification; D006526:Hepatitis C / Q000150:complications* / Q000821:virology; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D017422:Sequence Analysis, DNA; D014184:Transplantation, Homologous
chemical_list: D012367:RNA, Viral