TY - JOUR T1 - Tuning the course of evolution on the biophysical fitness landscape of an RNA virus JF - bioRxiv DO - 10.1101/090258 SP - 090258 AU - Assaf Rotem AU - Adrian W.R. Serohijos AU - Connie B. Chang AU - Joshua T. Wolfe AU - Audrey E. Fischer AU - Thomas S. Mehoke AU - Huidan Zhang AU - Ye Tao AU - W. Lloyd Ung AU - Jeong-Mo Choi AU - Abimbola O. Kolawole AU - Stephan A. Koehler AU - Susan Wu AU - Peter M. Thielen AU - Naiwen Cui AU - Plamen A. Demirev AU - Nicholas S. Giacobbi AU - Timothy R. Julian AU - Kellogg Schwab AU - Jeffrey S. Lin AU - Thomas J. Smith AU - James M. Pipas AU - Christiane E. Wobus AU - Andrew B. Feldman AU - David A. Weitz AU - Eugene I. Shakhnovich Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/11/28/090258.abstract N2 - Predicting viral evolution remains a major challenge with profound implications for public health. Viral evolutionary pathways are determined by the fitness landscape, which maps viral genotype to fitness. However, a quantitative description of the landscape and the evolutionary forces on it remain elusive. Here, we apply a biophysical fitness model based on capsid folding stability and antibody binding affinity to predict the evolutionary pathway of norovirus escaping a neutralizing antibody. The model is validated by experimental evolution in bulk culture and in a drop-based microfluidics device, the “Evolution Chip”, which propagates millions of independent viral sub-populations. We demonstrate that along the axis of binding affinity, selection for escape variants and drift due to random mutations have the same direction. However, along folding stability, selection and drift are opposing forces whose balance is tuned by viral population size. Our results demonstrate that predictable epistatic tradeoffs shape viral evolution. ER -