quasispecies spatial models for rna viruses with different replication modes and infection strategies准物种空间模型rna病毒感染不同的复制模式和策略.pdfVIP

Quasispecies Spatial Models for RNA Viruses with Different Replication Modes and Infection Strategies ´ 1 1,2 Josep Sardanyes *, Santiago F. Elena ´ ´ ` 1 Instituto de Biologıa Molecular y Celular de Plantas, Consejo Superior de Investigaciones Cientıficas, Valencia, Spain, 2 The Santa Fe Institute, Santa Fe, New Mexico, United States of America Abstract Empirical observations and theoretical studies suggest that viruses may use different replication strategies to amplify their genomes, which impact the dynamics of mutation accumulation in viral populations and therefore, their fitness and virulence. Similarly, during natural infections, viruses replicate and infect cells that are rarely in suspension but spatially organized. Surprisingly, most quasispecies models of virus replication have ignored these two phenomena. In order to study these two viral characteristics, we have developed stochastic cellular automata models that simulate two different modes of replication (geometric vs stamping machine) for quasispecies replicating and spreading on a two-dimensional space. Furthermore, we explored these two replication models considering epistatic fitness landscapes (antagonistic vs synergistic) and different scenarios for cell-to-cell spread, one with free superinfection and another with superinfection inhibition. We found that the master sequences for populations replicating geometrically and with antagonistic fitness effects vanished at low critical mutation rates. By contrast, the highest critical mutation rate was observed for populations replicating geometrically but with a synergistic fitness landscape. Our simulations also showed th