Mutagenic Effects of Ribavirin on Hepatitis E Virus-Viral Extinction versus Selection of Fitness-Enhancing Mutations.

2.50
Hdl Handle:
http://hdl.handle.net/10033/620584
Title:
Mutagenic Effects of Ribavirin on Hepatitis E Virus-Viral Extinction versus Selection of Fitness-Enhancing Mutations.
Authors:
Todt, Daniel; Walter, Stephanie; Brown, Richard J P; Steinmann, Eike
Abstract:
Hepatitis E virus (HEV), an important agent of viral hepatitis worldwide, can cause severe courses of infection in pregnant women and immunosuppressed patients. To date, HEV infections can only be treated with ribavirin (RBV). Major drawbacks of this therapy are that RBV is not approved for administration to pregnant women and that the virus can acquire mutations, which render the intra-host population less sensitive or even resistant to RBV. One of the proposed modes of action of RBV is a direct mutagenic effect on viral genomes, inducing mismatches and subsequent nucleotide substitutions. These transition events can drive the already error-prone viral replication beyond an error threshold, causing viral population extinction. In contrast, the expanded heterogeneous viral population can facilitate selection of mutant viruses with enhanced replication fitness. Emergence of these mutant viruses can lead to therapeutic failure. Consequently, the onset of RBV treatment in chronically HEV-infected individuals can result in two divergent outcomes: viral extinction versus selection of fitness-enhanced viruses. Following an overview of RNA viruses treated with RBV in clinics and a summary of the different antiviral modes of action of this drug, we focus on the mutagenic effect of RBV on HEV intrahost populations, and how HEV is able to overcome lethal mutagenesis.
Affiliation:
TWINCORE, Centre for experimental and clinical infection research GmbH, Feodor-Lynen Str. 7, 30625 Hannover, Germany.
Citation:
Mutagenic Effects of Ribavirin on Hepatitis E Virus-Viral Extinction versus Selection of Fitness-Enhancing Mutations. 2016, 8 (10) Viruses
Journal:
Viruses
Issue Date:
13-Oct-2016
URI:
http://hdl.handle.net/10033/620584
DOI:
10.3390/v8100283
PubMed ID:
27754363
Type:
Article
ISSN:
1999-4915
Appears in Collections:
publications of the research group virus transmission ([TC]VIRT)

Full metadata record

DC FieldValue Language
dc.contributor.authorTodt, Danielen
dc.contributor.authorWalter, Stephanieen
dc.contributor.authorBrown, Richard J Pen
dc.contributor.authorSteinmann, Eikeen
dc.date.accessioned2016-11-17T15:30:34Z-
dc.date.available2016-11-17T15:30:34Z-
dc.date.issued2016-10-13-
dc.identifier.citationMutagenic Effects of Ribavirin on Hepatitis E Virus-Viral Extinction versus Selection of Fitness-Enhancing Mutations. 2016, 8 (10) Virusesen
dc.identifier.issn1999-4915-
dc.identifier.pmid27754363-
dc.identifier.doi10.3390/v8100283-
dc.identifier.urihttp://hdl.handle.net/10033/620584-
dc.description.abstractHepatitis E virus (HEV), an important agent of viral hepatitis worldwide, can cause severe courses of infection in pregnant women and immunosuppressed patients. To date, HEV infections can only be treated with ribavirin (RBV). Major drawbacks of this therapy are that RBV is not approved for administration to pregnant women and that the virus can acquire mutations, which render the intra-host population less sensitive or even resistant to RBV. One of the proposed modes of action of RBV is a direct mutagenic effect on viral genomes, inducing mismatches and subsequent nucleotide substitutions. These transition events can drive the already error-prone viral replication beyond an error threshold, causing viral population extinction. In contrast, the expanded heterogeneous viral population can facilitate selection of mutant viruses with enhanced replication fitness. Emergence of these mutant viruses can lead to therapeutic failure. Consequently, the onset of RBV treatment in chronically HEV-infected individuals can result in two divergent outcomes: viral extinction versus selection of fitness-enhanced viruses. Following an overview of RNA viruses treated with RBV in clinics and a summary of the different antiviral modes of action of this drug, we focus on the mutagenic effect of RBV on HEV intrahost populations, and how HEV is able to overcome lethal mutagenesis.en
dc.languageENG-
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleMutagenic Effects of Ribavirin on Hepatitis E Virus-Viral Extinction versus Selection of Fitness-Enhancing Mutations.-
dc.typeArticleen
dc.contributor.departmentTWINCORE, Centre for experimental and clinical infection research GmbH, Feodor-Lynen Str. 7, 30625 Hannover, Germany.en
dc.identifier.journalVirusesen

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