Mechanisms of viral emergence

Domingo, Esteban

High mutation rates of RNA viruses and some DNA viruses result in dynamic distributions of mutants termed viral quasispecies ( Fig. 1 ). Viral quasispecies constitute reservoirs of genetic and phenotypic variants, with several biological implications for viral evolution and pathogenesis, some of which have become apparent over the last few years (reviews in [13, 14, 16, 25] ) (Tab. I). The main conceptual extension that quasispecies has represented for RNA virus genetics is that the ''wild type'' can no longer be assigned to a specific genomic nucleotide sequence but to a distribution of sequences. Mutation is not an occasional event but a continuously occurring event. When the consensus sequence is seen as invariant it is not because mutations did not occur but because they occurred in components of mutant spectrum without a change in the average or consensus sequence (Fig. 1 ). This is a key departure from classic genetics, and one of the fuels for viral disease emergences, since viral quasispecies may provide viral subpopulations ready to be selected in response to an environmental change, for example, an alternative host. As discussed below, the multi-phenotypic potential inherent to viral quasispecies represents a major driving force for viral disease emergence. In some cases, however a mutation reflected in the consensus (epidemic VEEV amplification in horses, expansion of influenza host range, etc.) may also serve as determinant of an emergence.