HEPATITIS-C VIRUS GENOMIC VARIABILITY IN UNTREATED AND IMMUNOSUPPRESSED PATIENTS

To investigate whether immune pressure enhances the genetic diversity of the hepatitis C virus (HCV) hypervariable region 1, nucleotide sequ ences were compared in multiple sera, collected longitudinally, from t hree untreated patients and four patients undergoing liver transplanta tion for HCV-related cirrhosis. A minor variant became dominant in thr ee of three patients following transplantation and persisted unchanged for months. Compared with untreated HCV carriers, transplant recipien ts had fewer quasispecies, fewer nucleotide changes (1.61 and 2.58/mon th), fewer amino acid sequence changes (0.40 and 1.94/month), as well as higher ratio of transitional to transversional mutations (2.57 and 0.98, P < 0.02) and lower replacement to silent mutations (1.33 and 8. 21, P < 0.01). The two patients with the least genomic variation died of HCV graft infection. The data suggest that HCV variants which infec t the graft are selected by recipient immune pressure at the time of t ransplant and that preferential replication in the graft is enhanced b y routine immunosuppression. (C) 1997 Academic Press.