Life cycle process dependencies of positive-sense RNA viruses suggest strategies for inhibiting productive cellular infection

Abstract

Life cycle processes of positive-strand (+)RNA viruses are broadly conserved across families, yet they employ different life cycle strategies to grow in the cell. Using a generalized dynamical model for intracellular (+)ssRNA virus growth, we decipher these life cycle determinants and their dependencies for several viruses and parse the effect of viral mutations and host cell permissivity. We show that Poliovirus employs rapid replication and virus assembly whereas Japanese Encephalitis virus leverages its higher rate of translation and efficient cellular reorganization compared to Hepatitis C virus. Stochastic simulations of the model demonstrate infection extinction if all seeding viral RNA degrade before establishing robust replication. The probability of productive cellular infection is affected by virus-host processes, defined by early life cycle events and viral seeding. Synergy among these parameters in limiting infection suggests new avenues for inhibiting viral infections by targeting early life cycle bottlenecks.