Rapid evolution of viral RNA genomes.

Mutation rates during RNA virus replication are several orders of magnitude larger than those operating during replication of cellular DNA. This results in the continuous generation of mutant genomes and in their rating in competition with other variants present and arising in the population. The dynamic mutant distributions that constitute RNA virus populations are termed quasispecies. This concept has facilitated links between population genetics and virology and has a number of important implications for viral pathogenesis and the control of viral disease. One of them is that the mutant spectra in RNA viruses constitute large reservoirs of genetic and phenotypic variants with potentially altered biological properties. Individual mutants kept in a low proportion under a set of environmental conditions may become dominant following an environmental change. Relevant to this review are possible links between the alteration of quasispecies distributions and nutritional deficiencies and oxidative stress in cells. In addition to being a possible mechanism of viral pathogenesis, oxidative stress, and other environmental modifications resulting from nutritional imbalances, may promote population disequilibrium in replicating viruses. In particular, the increased mutagenesis mediated by oxidative DNA damage could also affect replicating RNA and integrated provirus, extending the mutant repertoire of viruses. Also, the impairment of humoral and cellular immune functions may delay or prevent viral clearance, leading to an expanded representation of viral mutants in the infected organism. Thus, nutritional deficiencies are a potential source of viral mutants with altered biological properties.