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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.
Gastroenterology. 2014 Nov; 147(5):1008-11.e7; quiz e15-6.G

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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Authors+Show Affiliations

Debing Y
Rega Institute for Medical Research, Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium.
Gisa A
Department of Gastroenterology, Hepatology and Endocrinology, Center of Internal Medicine, Hannover Medical School, Hannover, Germany.
Dallmeier K
Rega Institute for Medical Research, Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium.
Pischke S
MVZ für Lebertransplantation, University Hospital Hamburg Eppendorf, Hamburg, Germany.
Bremer B
Department of Gastroenterology, Hepatology and Endocrinology, Center of Internal Medicine, Hannover Medical School, Hannover, Germany.
Manns M
Department of Gastroenterology, Hepatology and Endocrinology, Center of Internal Medicine, Hannover Medical School, Hannover, Germany.
Wedemeyer H
Department of Gastroenterology, Hepatology and Endocrinology, Center of Internal Medicine, Hannover Medical School, Hannover, Germany.
Suneetha PV
Department of Gastroenterology, Hepatology and Endocrinology, Center of Internal Medicine, Hannover Medical School, Hannover, Germany.
Neyts J
Rega Institute for Medical Research, Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium. Electronic address: johan.neyts@rega.kuleuven.be.

MeSH

Antiviral AgentsDNA-Directed RNA PolymerasesDose-Response Relationship, DrugDrug Resistance, ViralFemaleGenotypeHep G2 CellsHepatitis EHepatitis E virusHepatitis, ChronicHumansMaleMutagenesis, Site-DirectedMutationOrgan TransplantationPhenotypeRibavirinTime FactorsTransfectionTreatment FailureVirus Replication

Pub Type(s)

Journal Article
Video-Audio Media

Language

eng

PubMed ID

25181691

Citation

Debing, Yannick, et al. "A Mutation in the Hepatitis E Virus RNA Polymerase Promotes Its Replication and Associates With Ribavirin Treatment Failure in Organ Transplant Recipients." Gastroenterology, vol. 147, no. 5, 2014, pp. 1008-11.e7; quiz e15-6.
Debing Y, Gisa A, Dallmeier K, et al. A mutation in the hepatitis E virus RNA polymerase promotes its replication and associates with ribavirin treatment failure in organ transplant recipients. Gastroenterology. 2014;147(5):1008-11.e7; quiz e15-6.
Debing, Y., Gisa, A., Dallmeier, K., Pischke, S., Bremer, B., Manns, M., Wedemeyer, H., Suneetha, P. V., & Neyts, J. (2014). A mutation in the hepatitis E virus RNA polymerase promotes its replication and associates with ribavirin treatment failure in organ transplant recipients. Gastroenterology, 147(5), 1008-e7; quiz e15-6. https://doi.org/10.1053/j.gastro.2014.08.040
Debing Y, et al. A Mutation in the Hepatitis E Virus RNA Polymerase Promotes Its Replication and Associates With Ribavirin Treatment Failure in Organ Transplant Recipients. Gastroenterology. 2014;147(5):1008-11.e7; quiz e15-6. PubMed PMID: 25181691.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A mutation in the hepatitis E virus RNA polymerase promotes its replication and associates with ribavirin treatment failure in organ transplant recipients. AU - Debing,Yannick, AU - Gisa,Anett, AU - Dallmeier,Kai, AU - Pischke,Sven, AU - Bremer,Birgit, AU - Manns,Michael, AU - Wedemeyer,Heiner, AU - Suneetha,Pothakamuri Venkata, AU - Neyts,Johan, Y1 - 2014/08/30/ PY - 2014/06/06/received PY - 2014/07/31/revised PY - 2014/08/05/accepted PY - 2014/9/3/entrez PY - 2014/9/3/pubmed PY - 2015/1/31/medline KW - Drug Resistant KW - Mechanism KW - RNA-Dependent RNA Polymerase KW - Virulence SP - 1008-11.e7; quiz e15-6 JF - Gastroenterology JO - Gastroenterology VL - 147 IS - 5 N2 - 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. SN - 1528-0012 UR - https://www.unboundmedicine.com/medline/citation/25181691/A_mutation_in_the_hepatitis_E_virus_RNA_polymerase_promotes_its_replication_and_associates_with_ribavirin_treatment_failure_in_organ_transplant_recipients_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0016-5085(14)01079-8 DB - PRIME DP - Unbound Medicine ER -