RNA virus fitness.
RNA viruses constitute the most abundant group of pathogens of man, animals and plants. They share high mutation rates which are in the range 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 replicating RNA. Populations of RNA viruses are extremely heterogeneous and form dynamic mutant swarms termed viral quasispecies. This genetic organisation implies that any individual mutant has only a fleeting existence; that is, RNA viral genomes are statistically defined but individually indeterminate. RNA viruses are able to accommodate their average nucleotide sequences to changes in environment. A parameter used to quantitate adaptation is fitness, or the relative ability of a virus to produce infectious progeny. Repeated transfers of one or a few particles (bottleneck events) generally lead to fitness losses. In contrast, large population passages allow competitive optimisation of mutant genomes and fitness gains. Of relevance to medical practice is the ability of viral quasispecies to overcome selective pressures imposed by vaccines and antiviral agents. Particularly dramatic have been the systematic isolations of HIV-1 mutants resistant to antiretroviral inhibitors in treated individuals. In addition to the ability of HIV-1 quasispecies to generate many mutant genomes in short times, calculations of mutation frequencies in the pol gene of HIV-1 populations have documented that mutations related to resistance to antiretroviral inhibitors preexist 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 mutants resistant to the combination of antiviral agents. Copyright 1997 John Wiley & Sons, Ltd.
Domingo
E
Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Universidad Autónoma de Madrid, Cantoblanco, 28049-Madrid, Spain.
Menéndez-Arias
L
Holland
JJ