Viral Quasispecies and Lethal Mutagenesis

Abstract

Virology has undergone a profound transformation with the incorporation of quasispecies theory to the understanding of the composition and dynamics of viral populations as they cause disease. RNA viral populations do not consist of a genome class with a defined nucleotide sequence but of a cloud or swarm or related mutants due to high mutation rates (number of incorrect nucleotides introduced per nucleotide copied) during replication. DNA and RNA viruses whose multiplication is catalysed by a low fidelity polymerase replicate close to an error threshold for maintenance of their genetic information. This means that modest increases in mutation rate jeopardize their genetic stability. Realization of this important corollary of quasispecies theory has opened new approaches to combating viral disease. One of these approaches is lethal mutagenesis that consists of forcing virus extinction by an excess of mutations evoked by virus-specific mutagenic agents. This article summarizes the origin and current status of this new antiviral approach.