Genetic Meltdown

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Science  15 Jun 2001:
Vol. 292, Issue 5524, pp. 1969
DOI: 10.1126/science.292.5524.1969a

Ribavirin was identified as a broad-spectrum antiviral agent 30 years ago, but its mode of action remains obscure. Crotty et al. now show that the drug accelerates the already high mutation rate of RNA viruses (about 2 × 10−4) so as to precipitate a genomic crisis and ultimately to destroy the infectivity of the viral genomic RNA. This is possible because RNA viruses reside at the cusp of a phenomenon called error catastrophe. RNA viruses exist as an assemblage of related quasi-species that, because of their high inherent mutation rate, can adapt rapidly to new environments. Nevertheless, despite their rapid response capacity, this is a dangerous place to inhabit. There is a limit to how much variation a genome can tolerate without irretrievably degrading its genetic information. If a virus population is replicating at the brink, then just a bit of extra pressure from a mutagen, such as ribavirin, may push it into the abyss of genetic meltdown, resulting in an inability to replicate and loss of viability. — CA

Proc. Natl. Acad. Sci. U.S.A.98, 6895 (2001).

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