Journal
DRUG RESISTANCE UPDATES
Volume 7, Issue 1, Pages 19-24Publisher
CHURCHILL LIVINGSTONE
DOI: 10.1016/j.drup.2003.12.003
Keywords
RNA virus; antiviral agent; ribavirin; lethal mutagenesis; error catastrophe; RNA-dependent RNA polymerase; poliovirus; coxsackievirus B3; hepatitis C virus
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Funding
- NIAID NIH HHS [AI 54776] Funding Source: Medline
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RNA virus populations display extreme sequence variation. It is thought that this heterogeneity is advantageous to the population, permitting adaptation to rapidly changing environments that present varying types and degrees of selective pressure. A consequence of this efficient evolution of RNA viruses is the susceptibility of these viruses to compounds that further increase sequence variation as these agents force the virus into error catastrophe. Therefore, lethal mutagenesis, induction of error catastrophe, represents an important, untapped strategy for development of antiviral agents. This article briefly describes the theoretical and experimental data supporting lethal mutagenesis as an antiviral strategy and discusses host and viral mechanisms for development of resistance to ribavirin, a representative of this class of antiviral agents. (C) 2004 Elsevier Ltd. All rights reserved.
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