A speed-fidelity trade-off determines the mutation rate and virulence of an RNA virus

William Fitzsimmons; Robert J. Woods; John T. McCrone; Andrew Woodman; Jamie J. Arnold; Madhumita Yennawar; Richard Evans; Craig E. Cameron; Adam S. Lauring

The absence of mutational diversity in our replicate WT and 3D G64S stocks is important, as 211 poliovirus populations are subject to stringent bottleneck events, which further restrict intrahost 212 diversity [48] [49] [50] . Work with barcoded RNA viruses suggests that the serial bottlenecks between 213 the infecting population and the terminal population colonizing the central nervous system 214 (CNS) are quite stringent [51, 52] , and we used published data to quantify the aggregate 215 bottleneck size encountered by poliovirus in transgenic mice [45, 48, 49] . Maximum likelihood 216 optimization of a simple probabilistic model estimated an aggregate bottleneck size of 2.67 217 between the inoculum and the CNS (Fig. 4A , SI Model 2). Therefore, the population that causes 218 eventual disease in these mice is derived from no more than 2-3 viruses in the infecting 219 population. In the setting of tight bottlenecks, many mutations will increase in frequency due to 220 genetic drift as opposed to positive selection.