NDLI: A single mutation in poliovirus RNA-dependent RNA polymerase confers resistance to mutagenic nucleotide analogs via increased fidelity.

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A single mutation in poliovirus RNA-dependent RNA polymerase confers resistance to mutagenic nucleotide analogs via increased fidelity.

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A single mutation in poliovirus RNA-dependent RNA polymerase confers resistance to mutagenic nucleotide analogs via increased fidelity.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Kirkegaard, Karla Pfeiffer, Julie K.
Description	Author Affiliation: Pfeiffer JK ( Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.);
Abstract	Ribavirin is a nucleotide analog that can be incorporated by viral polymerases, causing mutations by allowing base mismatches. It is currently used therapeutically as an antiviral drug during hepatitis C virus infections. During the amplification of poliovirus genomic RNA or hepatitis C replicons, error frequency is known to increase upon ribavirin treatment. This observation has led to the hypothesis that ribavirin's antiviral activity results from error catastrophe caused by increased mutagenesis of viral genomes. Here, we describe the generation of ribavirin-resistant poliovirus by serial viral passage in the presence of increasing concentrations of the drug. Ribavirin resistance can be caused by a single amino acid change, G64S, in the viral polymerase in an unresolved portion of the fingers domain. Compared with wild-type virus, ribavirin-resistant poliovirus displays increased fidelity of RNA synthesis in the absence of ribavirin and increased survival both in the presence of ribavirin and another mutagen, 5-azacytidine. Ribavirin-resistant poliovirus represents an unusual class of viral drug resistance: resistance to a mutagen through increased fidelity.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	12
Volume Number	100
Language	English
Publisher	National Academy of Sciences
Publisher Date	2003-06-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Point Mutation Poliovirus Enzymology Genetics RNA Replicase Antiviral Agents Pharmacology DNA, Viral Drug Resistance, Viral HeLa Cells Models, Molecular Drug Effects Chemistry RNA, Viral Biosynthesis Ribavirin Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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