<![CDATA[<B>CD<SUB>81</SUB> binding regions of hepatitis C virus remain conserved after liver transplantation</B>]]>

Abstract

CD 81 is a surface-associated protein expressed in the membranes of mammalian cells. It has been suggested that CD 81 interacts with hepatitis C virus E2 protein, and thus might facilitate the entry of HCV into hepatocytes. The envelope-binding site appears to involve amino acids (aa) 480-493 and 544-551 within the E2 glycoprotein. Little is known about the quasispecies genetic diversity of these two regions. We studied four patients who underwent transplantation for HCVrelated cirrhosis and who developed recurrent hepatitis C. We evaluated HCV quasispecies diversity in serum samples obtained at the time of transplantation and at several time points thereafter. Quasispecies diversity was assessed by cloning and sequencing of viral isolates, with computer analysis of evolution models. The genetic distance in the region that spans aa 480 to 493 was 0.019 ± 0.004 before the transplant, and 0.039 ± 0.014 after the transplant (p=0.324). In the aa 544 to 551 region, the pre-transplant genetic distance was 0.012 ± 0.008 and the post-transplant distance, 0.010 ± 0.007 (p=0.890). There was also no significant difference between the number of nonsynonymous substitutions per nonsynonymous site before and after transplantation. In conclusion, the HCV genetic sequences of putative CD 81 binding regions aa 480-493 and aa 544-551 did not diversify significantly after liver transplantation. This may favor HCV re-infection of the allograft after liver transplantation.

NK Cells, Innate Immunity and Hepatitis C Infection after Liver Transplantation

“…The timing of this process suggests, rather than an immune process or selection based on relative replicative efficiency, that the nature of posttransplant infection is determined by competition of quasispecies for viral entry. Studies of quasispecies pretransplant, postperfusion, and postallograft infection suggest that the allograft selects a fraction of the quasispecies variants found in serum and that posttransplant evolution of this fraction retains conservation of the E2 residues [41][42][43][44][45][46]. This conservation suggests a role for the interaction between E2 and specific allograft receptors in the development of posttransplant HCV infection.…”