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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

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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. / Debing, Yannick; Gisa, Anett; Dallmeier, Kai; Pischke, Sven; Bremer, Birgit; Manns, Michael; Wedemeyer, Heiner; Suneetha, Pothakamuri Venkata; Neyts, Johan.

In: GASTROENTEROLOGY, Vol. 147, No. 5, 01.11.2014, p. 1008-1011.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Debing, Y, Gisa, A, Dallmeier, K, Pischke, S, Bremer, B, Manns, M, Wedemeyer, H, Suneetha, PV & 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, vol. 147, no. 5, pp. 1008-1011. https://doi.org/10.1053/j.gastro.2014.08.040

APA

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), 1008-1011. https://doi.org/10.1053/j.gastro.2014.08.040

Vancouver

Debing Y, Gisa A, Dallmeier K, Pischke S, Bremer B, Manns M 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 Nov 1;147(5):1008-1011. https://doi.org/10.1053/j.gastro.2014.08.040

Bibtex

@article{c086b490b803490c821d3a9807c3b81e,
title = "A mutation in the hepatitis E virus RNA polymerase promotes its replication and associates with ribavirin treatment failure in organ transplant recipients",
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.",
keywords = "Antiviral Agents, DNA-Directed RNA Polymerases, Dose-Response Relationship, Drug, Drug Resistance, Viral, Female, Genotype, Hep G2 Cells, Hepatitis E, Hepatitis E virus, Hepatitis, Chronic, Humans, Male, Mutagenesis, Site-Directed, Mutation, Organ Transplantation, Phenotype, Ribavirin, Time Factors, Transfection, Treatment Failure, Virus Replication",
author = "Yannick Debing and Anett Gisa and Kai Dallmeier and Sven Pischke and Birgit Bremer and Michael Manns and Heiner Wedemeyer and Suneetha, {Pothakamuri Venkata} and Johan Neyts",
note = "Copyright {\textcopyright} 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.",
year = "2014",
month = nov,
day = "1",
doi = "10.1053/j.gastro.2014.08.040",
language = "English",
volume = "147",
pages = "1008--1011",
journal = "GASTROENTEROLOGY",
issn = "0016-5085",
publisher = "W.B. Saunders Ltd",
number = "5",

}

RIS

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

N1 - Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

PY - 2014/11/1

Y1 - 2014/11/1

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.

AB - 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.

KW - Antiviral Agents

KW - DNA-Directed RNA Polymerases

KW - Dose-Response Relationship, Drug

KW - Drug Resistance, Viral

KW - Female

KW - Genotype

KW - Hep G2 Cells

KW - Hepatitis E

KW - Hepatitis E virus

KW - Hepatitis, Chronic

KW - Humans

KW - Male

KW - Mutagenesis, Site-Directed

KW - Mutation

KW - Organ Transplantation

KW - Phenotype

KW - Ribavirin

KW - Time Factors

KW - Transfection

KW - Treatment Failure

KW - Virus Replication

U2 - 10.1053/j.gastro.2014.08.040

DO - 10.1053/j.gastro.2014.08.040

M3 - SCORING: Journal article

C2 - 25181691

VL - 147

SP - 1008

EP - 1011

JO - GASTROENTEROLOGY

JF - GASTROENTEROLOGY

SN - 0016-5085

IS - 5

ER -