Viral Error Catastrophe by Mutagenic Nucleosides

Author:

Anderson Jon P.1,Daifuku Richard2,Loeb Lawrence A.1

Affiliation:

1. The Joseph Gottstein Memorial Cancer Research Laboratory, Departments of Pathology and Biochemistry, University of Washington, Seattle, Washington 98195;

2. Koronis Pharmaceuticals, Redmond, Washington 98052;

Abstract

▪ Abstract  Riboviruses and retroviruses have the highest rates of mutations of any known organism. Increasing the mutation rate of these viruses could exceed the error threshold for viability of a viral population within a host. Recent experiments with mutagenic nucleoside analogs validate this new approach to treating infection of RNA viruses. Lethal mutagenesis with HIV-infected cells in culture has been documented and has been postulated to be the mechanism for treatment of hepatitis C with ribavirin. We consider the viral dynamics involved in the formation of a quasispecies, the choice of mutagenic nucleoside analogs, and the studies that have demonstrated the feasibility of lethal mutagenesis.

Publisher

Annual Reviews

Subject

Microbiology

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