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A Mutation in the Hepatitis E Virus RNA Polymerase Promotes its Replication and Associates With Ribavirin Treatment Failure in Organ Transplant Recipients

Authors
Journal
Gastroenterology
0016-5085
Publisher
Elsevier
Identifiers
DOI: 10.1053/j.gastro.2014.08.040
Keywords
  • Rna-Dependent Rna Polymerase
  • Virulence
  • Drug Resistant
  • Mechanism
Disciplines
  • Biology
  • Medicine

Abstract

We analyzed blood samples collected from 15 patients with chronic hepatitis E who were recipients of solid-organ transplants. All patients cleared the hepatitis E virus (HEV) except for 2 (nonresponders); 1 patient died. A G1634R mutation in viral polymerase was detected in the HEV RNA of the nonresponders; this mutation did not provide the virus with resistance to ribavirin in vitro. However, the mutant form of a subgenomic replicon of genotype 3 HEV replicated more efficiently in vitro than HEV without this mutation, and the same was true for infectious virus, including in competition assays. Similar results were obtained for genotype 1 HEV. The G1634R mutation therefore appears to increase the replicative capacity of HEV in the human liver and hence reduce the efficacy of ribavirin.

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