Key result
Stochastic simulations of positive-strand RNA virus growth demonstrate that infection extinction occurs if all seeding viral RNA degrade before establishing robust replication.
Why the study?
Life cycle processes of positive-strand RNA viruses are broadly conserved across families, yet they employ different strategies to grow intracellularly.
A generalized dynamical model of (+)RNA virus life cycles reveals that targeting early events like membrane reorganization and viral RNA degradation synergistically inhibits productive cellular infection.
Animal models suggest targeting early RNA degradation may block viral infection; leaves open clinical translation pending human studies.
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.
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Chhajer et al. (2020) studied Positive-strand (+)RNA virus infection. Dynamical modeling and stochastic simulations was evaluated on Probability of productive cellular infection and infection extinction. Stochastic simulations of positive-strand RNA virus growth demonstrate that infection extinction occurs if all seeding viral RNA degrade before establishing robust replication.
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