RNA VIRUS QUASI-SPECIES - SIGNIFICANCE FOR VIRAL DISEASE AND EPIDEMIOLOGY

The experimental evidence available for animal and plant RNA viruses, as well as other RNA genetic elements (viroids, satellites, retroeleme nts, etc.), reinforces the view that many different types of genetic a lterations may occur during RNA genome replication. This is fundamenta lly because of infidelity of genome replication and large population s izes. Homologous and heterologous recombination, as well as gene reass ortments occur frequently during replication of retroviruses and most riboviruses, especially those that use enzymes with limited processivi ty. Following the generation of variant genomes, selection, which is d ependent on environmental parameters in ways that are poorly understoo d, sorts out those genome fits enough to generate viable quasispecies. Chance events can also be destabilizing, as illustrated by recent res ults on fitness loss and other phenotypic changes accompanying bottlen eck transmission. Variation, selection, and random sampling of genomes occur continuously and unavoidably during virus evolution. Evolution of RNA viruses is largely unpredictable because of the stochastic natu re of mutation and recombination events, as well as the subtle effects of chance transmission events and host/environmental factors. Among e nvironmental factors, alterations resulting from human intervention (d eforestation, agricultural activities, global climatic changes, etc.) may alter dispersal patterns and provide new adaptive possibilities to viral quasispecies. Current understanding of RNA virus evolution sugg ests several strategies to control and diagnose viral diseases. The ne w generation of chemically defined vaccines and diagnostic reagents (m onoclonal antibodies, peptide antigens, oligonucleotides for polymeras e chain reaction amplification, etc.) may be adequate to prevent disea se and detect some or even most of the circulating quasispecies of any given RNA pathogen. However, the dynamics of viral quasispecies manda te careful consideration of those reagents to be incorporated into dia gnostic kits. Broadening diagnosis without jeopardizing specificity of detection will be challenging. There is a finite probability (impossi ble to quantify at present) that a defined vaccine may promote selecti on of escape mutants or a particular diagnostic kit may fail to detect a viral pathogen. Of particular concern are the potential long-term e ffects of weak selective pressures that may initially go unnoticed. Va riant viruses resulting from evolutionary pressure imposed by vaccines or drugs may insidiously and gradually replace previous quasispecies. The great potential for variation and phenotypic diversity of some im portant RNA virus pathogens (human immunodeficiency virus, the hepatit is viruses, the newly recognized human hantaviruses, etc.) has become clear. Prevention and therapy should rely on multicomponent vaccines a nd antiviral agents to address the complexity of RNA quasispecies muta nt spectra. This will require additional vaccine antigens and larger r epertoires of drugs directed at multiple viral targets. Finally, new a venues of research, such as molecular approaches to promote error cata strophe during viral replication, should also be undertaken. Basic stu dies on quasispecies and on population genetics of RNA viruses are jus tified not only by their relevance to the understanding of viral evolu tion but also by their direct implications for viral pathogenesis and for strategies of disease control.