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In vivo evidence for ribavirin-induced mutagenesis of the hepatitis E virus genome

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In vivo evidence for ribavirin-induced mutagenesis of the hepatitis E virus genome. / Todt, Daniel; Gisa, Anett; Radonic, Aleksandar; Nitsche, Andreas; Behrendt, Patrick; Suneetha, Pothakamuri Venkata; Pischke, Sven; Bremer, Birgit; Brown, Richard J P; Manns, Michael P; Cornberg, Markus; Bock, C Thomas; Steinmann, Eike; Wedemeyer, Heiner.

in: GUT, Jahrgang 65, Nr. 10, 10.2016, S. 1733-43.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Todt, D, Gisa, A, Radonic, A, Nitsche, A, Behrendt, P, Suneetha, PV, Pischke, S, Bremer, B, Brown, RJP, Manns, MP, Cornberg, M, Bock, CT, Steinmann, E & Wedemeyer, H 2016, 'In vivo evidence for ribavirin-induced mutagenesis of the hepatitis E virus genome', GUT, Jg. 65, Nr. 10, S. 1733-43. https://doi.org/10.1136/gutjnl-2015-311000

APA

Todt, D., Gisa, A., Radonic, A., Nitsche, A., Behrendt, P., Suneetha, P. V., Pischke, S., Bremer, B., Brown, R. J. P., Manns, M. P., Cornberg, M., Bock, C. T., Steinmann, E., & Wedemeyer, H. (2016). In vivo evidence for ribavirin-induced mutagenesis of the hepatitis E virus genome. GUT, 65(10), 1733-43. https://doi.org/10.1136/gutjnl-2015-311000

Vancouver

Todt D, Gisa A, Radonic A, Nitsche A, Behrendt P, Suneetha PV et al. In vivo evidence for ribavirin-induced mutagenesis of the hepatitis E virus genome. GUT. 2016 Okt;65(10):1733-43. https://doi.org/10.1136/gutjnl-2015-311000

Bibtex

@article{bd7fe1f2e25b400d920fa4ea56e5b985,
title = "In vivo evidence for ribavirin-induced mutagenesis of the hepatitis E virus genome",
abstract = "OBJECTIVE: Hepatitis E virus (HEV) infection can take chronic courses in immunocompromised patients potentially leading to liver cirrhosis and liver failure. Ribavirin (RBV) is currently the only treatment option for many patients, but treatment failure can occur which has been associated with the appearance of a distinct HEV polymerase mutant (G1634R). Here, we performed a detailed analysis of HEV viral intrahost evolution during chronic hepatitis E infections.DESIGN: Illumina deep sequencing was performed for the detection of intrahost variation in the HEV genome of chronically infected patients. Novel polymerase mutants were investigated in vitro using state-of-the-art HEV cell culture models.RESULTS: Together, these data revealed that (1) viral diversity differed markedly between patients but did not show major intraindividual short-term variations in untreated patients with chronic hepatitis E, (2) RBV therapy was associated with an increase in viral heterogeneity which was reversible when treatment was stopped, (3) the G1634R mutant was detectable as a minor population prior to therapy in patients who subsequently failed to achieve a sustained virological response to RBV therapy and (4) in addition to G1634R further dominant variants in the polymerase region emerged, impacting HEV replication efficiency in vitro.CONCLUSIONS: In summary, this first investigation of intrahost HEV population evolution indicates that RBV causes HEV mutagenesis in treated patients and that an emergence of distinct mutants within the viral population occurs during RBV therapy. We also suggest that next-generation sequencing could be useful to guide personalised antiviral strategies.",
keywords = "Journal Article",
author = "Daniel Todt and Anett Gisa and Aleksandar Radonic and Andreas Nitsche and Patrick Behrendt and Suneetha, {Pothakamuri Venkata} and Sven Pischke and Birgit Bremer and Brown, {Richard J P} and Manns, {Michael P} and Markus Cornberg and Bock, {C Thomas} and Eike Steinmann and Heiner Wedemeyer",
note = "Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/",
year = "2016",
month = oct,
doi = "10.1136/gutjnl-2015-311000",
language = "English",
volume = "65",
pages = "1733--43",
journal = "GUT",
issn = "0017-5749",
publisher = "BMJ PUBLISHING GROUP",
number = "10",

}

RIS

TY - JOUR

T1 - In vivo evidence for ribavirin-induced mutagenesis of the hepatitis E virus genome

AU - Todt, Daniel

AU - Gisa, Anett

AU - Radonic, Aleksandar

AU - Nitsche, Andreas

AU - Behrendt, Patrick

AU - Suneetha, Pothakamuri Venkata

AU - Pischke, Sven

AU - Bremer, Birgit

AU - Brown, Richard J P

AU - Manns, Michael P

AU - Cornberg, Markus

AU - Bock, C Thomas

AU - Steinmann, Eike

AU - Wedemeyer, Heiner

N1 - Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

PY - 2016/10

Y1 - 2016/10

N2 - OBJECTIVE: Hepatitis E virus (HEV) infection can take chronic courses in immunocompromised patients potentially leading to liver cirrhosis and liver failure. Ribavirin (RBV) is currently the only treatment option for many patients, but treatment failure can occur which has been associated with the appearance of a distinct HEV polymerase mutant (G1634R). Here, we performed a detailed analysis of HEV viral intrahost evolution during chronic hepatitis E infections.DESIGN: Illumina deep sequencing was performed for the detection of intrahost variation in the HEV genome of chronically infected patients. Novel polymerase mutants were investigated in vitro using state-of-the-art HEV cell culture models.RESULTS: Together, these data revealed that (1) viral diversity differed markedly between patients but did not show major intraindividual short-term variations in untreated patients with chronic hepatitis E, (2) RBV therapy was associated with an increase in viral heterogeneity which was reversible when treatment was stopped, (3) the G1634R mutant was detectable as a minor population prior to therapy in patients who subsequently failed to achieve a sustained virological response to RBV therapy and (4) in addition to G1634R further dominant variants in the polymerase region emerged, impacting HEV replication efficiency in vitro.CONCLUSIONS: In summary, this first investigation of intrahost HEV population evolution indicates that RBV causes HEV mutagenesis in treated patients and that an emergence of distinct mutants within the viral population occurs during RBV therapy. We also suggest that next-generation sequencing could be useful to guide personalised antiviral strategies.

AB - OBJECTIVE: Hepatitis E virus (HEV) infection can take chronic courses in immunocompromised patients potentially leading to liver cirrhosis and liver failure. Ribavirin (RBV) is currently the only treatment option for many patients, but treatment failure can occur which has been associated with the appearance of a distinct HEV polymerase mutant (G1634R). Here, we performed a detailed analysis of HEV viral intrahost evolution during chronic hepatitis E infections.DESIGN: Illumina deep sequencing was performed for the detection of intrahost variation in the HEV genome of chronically infected patients. Novel polymerase mutants were investigated in vitro using state-of-the-art HEV cell culture models.RESULTS: Together, these data revealed that (1) viral diversity differed markedly between patients but did not show major intraindividual short-term variations in untreated patients with chronic hepatitis E, (2) RBV therapy was associated with an increase in viral heterogeneity which was reversible when treatment was stopped, (3) the G1634R mutant was detectable as a minor population prior to therapy in patients who subsequently failed to achieve a sustained virological response to RBV therapy and (4) in addition to G1634R further dominant variants in the polymerase region emerged, impacting HEV replication efficiency in vitro.CONCLUSIONS: In summary, this first investigation of intrahost HEV population evolution indicates that RBV causes HEV mutagenesis in treated patients and that an emergence of distinct mutants within the viral population occurs during RBV therapy. We also suggest that next-generation sequencing could be useful to guide personalised antiviral strategies.

KW - Journal Article

U2 - 10.1136/gutjnl-2015-311000

DO - 10.1136/gutjnl-2015-311000

M3 - SCORING: Journal article

C2 - 27222534

VL - 65

SP - 1733

EP - 1743

JO - GUT

JF - GUT

SN - 0017-5749

IS - 10

ER -