Multiple infection dynamics has pronounced effects on the fitness of RNA viruses

Several factors play a role during the replication and transmission of RNA viruses. First, as a consequence of their enormous mutation rate, complex m ixtures of genomes are generated immediately after infection of a new host. Secondly, differences in growth and competition rates drive the selection of certain genetic variants within an infected host. Thirdly, but not less important, a random sampling occurs at the moment of viral infectious passa ge from an infected to a healthy host. In addition, the availability of hos ts also influences the fate of a given viral genotype. When new hosts are s carce, different viral genotypes might infect the same host, adding an extr a complexity to the competition among genetic variants. We have employed a two-fold approach to analyse the role played by each of these factors in th e evolution of RNA viruses. First, we have derived a model that takes into account all the preceding factors. This model employs the classic Lotka-Vol terra competition equations but it also incorporates the effect of mutation during RNA replication, the effect of the stochastic sampling at the momen t of infectious passage among hosts and, the effect of the type of infectio n (single, coinfection or superinfection). Secondly, the predictions of the model have been tested in an in vitro evolution experiment. Both theoretic al and experimental results show that in infection passages with coinfectio n viral fitness increased more than in single infections. In contrast, infe ction passages with superinfection did not differ from the single infection . The coinfection frequency also affected the outcome: the larger the propo rtion of viruses coinfecting a host, the larger increase in fitness observe d.