The impact of immunosuppression on nucleotide sequence diversity in the first hypervariable region (HVR1) of hepatitis C virus (HCV).
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Elektronische Ressource
Hepatitis C virus (HCV) is responsible for most cases of non-A, non-B hepatitis. The persistent nature of this virus has been attributed to viral replication errors, which lead to a dynamic pool of antigenic variants that allow escape from the host immune response. A major part of this escape is due to the hypervariable region 1 (HVR1) of HCV, known to encode structurally flexible, isolate-specific neutralising epitopes which undergo successive genetic alterations. In a substantial number of cases, complications of HCV infection lead to end-stage liver disease for which the only treatment is orthotopic liver transplantation (OLT). Primary HCV infection of the allograft is an almost universal phenomenon associated with OLT. This study focused on the pattern of HCV variability in the context of immunosuppression, which is a feature of post-OLT treatment. Sequences of the HCV HVR1 derived from OLT recipients and from asymptomatic (presumably immunocompetent) carriers of the virus were compared over several time-points. A rapid turnover of sequences was found in the untreated subjects, in whom mean nucleotide and amino acid sequence diversity were 19.8% and 43.5%, respectively. In the immunosuppressed patients, the corresponding figures were 2.3% and 2.3%. Untreated subjects showed a ratio of transitional to transversional mutations of 2.57, compared with 0.98 for untreated subjects (p = 0.0165). Similarly, the replacement to silent mutation (R/S) ratios were 8.22 and 1.33 (p = 0.0069), respectively. The major differences between the two groups of patients were especially demonstrated by a subset of two immunosuppressed patients, in whom the HVRl showed almost 100% homogeneity throughout a year of follow-up. Both patients required re-transplantation within a year of the first OLT, and both died of HCV-related disease shortly afterwards. On the other hand, two other transplant recipients, who showed an HVRl mutation rate indistinguishable from that found in the untreated
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The impact of immunosuppression on nucleotide sequence diversity in the first hypervariable region (HVR1) of hepatitis C virus (HCV).
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Medientyp: | Elektronische Ressource |
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