RNA VIRUS FITNESS

RNA viruses constitute the most abundant group of pathogens of man, an imals and plants. They share high mutation rates which are in the rang e 10(-3) to 10(-5) misincorporations per nucleotide site and round of copying. This is due to the absence or low efficiency of proofreading- repair or postreplicative repair activities associated with replicatin g RNA. Populations of RNA viruses are extremely heterogeneous and form dynamic mutant swarms termed viral quasispecies. This genetic organis ation implies that any individual mutant has only a fleeting existence ; that is, RNA viral genomes are statistically defined but individuall y indeterminate. RNA viruses are able to accommodate their average nuc leotide sequences to changes in environment. A parameter used to quant itate adaptation is fitness, or the relative ability of a virus to pro duce infectious progeny. Repeated transfers of one or a few particles (bottleneck events) generally lead to fitness losses. In contrast, lar ge population passages allow competitive optimisation of mutant genome s and fitness gains. Of relevance to medical practice is the ability o f viral quasispecies to overcome selective pressures imposed by vaccin es and antiviral agents. particularly dramatic have been the systemati c isolations of HIV-1 mutants resistant to antiretroviral inhibitors i n treated individuals. In addition to the ability of HIV-1 quasispecie s to generate many mutant genomes in short times, calculations of muta tion frequencies in the pol gene of HIV-1 populations have documented that mutations related to resistance to antiretroviral inhibitors pree xist in the mutant swarms of HIV-1 quasispecies. It is not possible at present to anticipate whether a suitable drug cocktail may be capable of sustained inhibition of HIV-1 replication without selection of mut ants resistant to the combination of antiviral agents. (C) 1997 by Joh n Wiley & Sons, Ltd.