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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.
- Source :
-
Gastroenterology [Gastroenterology] 2014 Nov; Vol. 147 (5), pp. 1008-11.e7; quiz e15-6. Date of Electronic Publication: 2014 Aug 30. - Publication Year :
- 2014
-
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.<br /> (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Dose-Response Relationship, Drug
Drug Resistance, Viral genetics
Female
Genotype
Hep G2 Cells
Hepatitis E diagnosis
Hepatitis E mortality
Hepatitis E virology
Hepatitis E virus enzymology
Hepatitis E virus genetics
Hepatitis E virus growth & development
Hepatitis, Chronic diagnosis
Hepatitis, Chronic mortality
Hepatitis, Chronic virology
Humans
Male
Mutagenesis, Site-Directed
Phenotype
Time Factors
Transfection
Treatment Failure
Virus Replication genetics
Antiviral Agents therapeutic use
DNA-Directed RNA Polymerases genetics
Hepatitis E drug therapy
Hepatitis E virus drug effects
Hepatitis, Chronic drug therapy
Mutation
Organ Transplantation adverse effects
Ribavirin therapeutic use
Virus Replication drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0012
- Volume :
- 147
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Gastroenterology
- Publication Type :
- Academic Journal
- Accession number :
- 25181691
- Full Text :
- https://doi.org/10.1053/j.gastro.2014.08.040