Population Complexity of Replicating Genomes : Viral Quasispecies

The emergence and reemergence of infectious diseases is influenced by the genetics of the infectious agents, the genetics of their hosts and potential new host species, and a considerable number of environmental factors (1-3). The current view proposes a strong stochastic (chance) component regarding the time, place, severity, and epidemiologic impact of infectious disease emergences (2,3). For RNA and possibly some DNA viruses, increasing evidence suggests that genetic variation (mutation, recombination, and genome segment reassortment in the case of multipartite genomes) affects adaptability to environmental changes (4-9). Since some types of adaptation involve changes in host cell specificity (5,6,10), genetic variation of viruses may be involved in the emergence of pathogenic viruses from apathogenic ancestors. Many studies over the last 2 decades have documented the unpredictability of genetic variation in viruses (2,5-7). In this report, we consider viral persistence in connection with the population structure of RNA viruses, specifically, the extension (in space and time) of the pool of replicating genomes, which are a potential source of variant viruses with altered biologic features. For example, hantaviruses are apathogenic and endogenous to several rodent species. In several geographic areas of the American continent, the unusually mild and wet (El Niño effect) spring seasons of 1992 and 1993 resulted in abundant food and coverage for deer mice, increased numbers of infected deer mice, and increased risk for human infections. These factors led to the newly recognized severe pulmonary syndrome of humans in 1993 (11). Like many pathogenic RNA viruses, hantavirus evolved in humans, and recent epidemiologic evidence suggests humanto-human transmission (12); whether human-tohuman transmission is exceedingly rare or is an unusual property associated with Andes virus is not known. The number of carriers, their ability to transport virus (because of their mobility and absence of severe symptoms), and the viral load (number and concentration of infectious particles) in each carrier must be involved in viral emergences and reemergences (2-4,6,13).