Quasispecies diversity determines pathogenesis through cooperative interactions in a viral population

摘要: The replication of RNA viruses is associated with a higher mutation rate than seen in organisms using DNA as their genetic material. This can produce nonviable individuals but also, it has been suggested, some useful variation that could enhance the fitness virus populations by allowing them to adapt changing environments encountered during infection. Until now there no experimental support for this suggestion, known ‘quasispecies’ hypothesis. But search copy genome too accurately provided idea. Poliovirus isolates carrying ‘super accurate’ polymerase are less varied and infectious normal viruses. These results have implications development antiviral drugs. An population does not consist single genotype; rather, an ensemble related sequences, termed quasispecies1,2,3,4. Quasispecies arise from rapid genomic evolution powered high viral replication5,6,7,8. Although dangerous because individuals, hypothesized rates create ‘cloud’ potentially beneficial mutations at level, which afford quasispecies greater probability evolve new challenges infection4,9,10,11. Mathematical models predict simply collection diverse mutants group interactive variants, together contribute characteristics population4,12. According view, populations, rather individual target evolutionary selection4,12. Here we test hypothesis examining consequences limiting diversity on populations. We find poliovirus high-fidelity replicates wild-type levels generates unable adverse growth conditions. In infected animals, reduced leads loss neurotropism attenuated pathogenic phenotype. Notably, chemical mutagenesis expand before infection restores pathogenesis. Analysis isolated brain provides direct evidence complementation between members quasispecies, indicating selection indeed occurs level variants. Our study fundamental prediction theory establishes link rate, dynamics