Stress Testing Complete Kinetic Models of Individualized Enteroviral Infection

Enteroviruses are responsible for a wide array of human diseases, including viral myocarditis, infantile paralysis, hand-foot-and-mouth disease, and the common cold. The enteroviral RNA genome is small, and the single polyprotein it encodes is sufficient to infect permissive host cells within a matter of hours. Since research on cultured enteroviruses began in 1949, we have accumulated a wealth of quantitative information about their biochemistry, cell biology, and genetics. By comparison, there have been only limited attempts to synthesize this information holistically through mathematical modeling and analysis. We recently built a complete kinetic model for coxsackievirus B3 (CVB3), an enterovirus that infects cardiomyocytes to cause heart inflammation and failure (Cell Syst 123:304-23 [2021]). The model encodes detailed mechanisms for three modular pillars of the viral life cycle—host-cell delivery, translation–replication, and encapsidation - along with host-cell antiviral feedbacks that are antagonized during infection. Over 90% of the numbers parameterizing the rate equations are drawn directly from the literature or our own experiments. Model simulations captured the kinetics of infection and made predictions about host-cell susceptibilities that were later verified. Although useful, the model’s construction revealed several unknowns about the critical early steps of enteroviral infection. In this presentation, I will present ideas for a grant proposal that seeks to tackle the uncertainties head-on by integrating quantitative experiments with mathematical revisions that “stress test” the model to adapt for more-generalized applications. In doing so, we hypothesize that more detail will yield more insight about open questions in enterovirology. For more details see: https://www.sciencedirect.com/science/article/pii/S2405471221000788 Compositional Modelling of Adaptive Immune Response to and Disease Transmission of SARS-CoV-2 William Waites University of Strathclyde We show how a simple stochastic model of adaptive immune response recovers individual heterogeneity in viral load in a population. This model can be easily coupled to a transmission model from which we can observe the changing distributions of viral load over the course of an epidemic. This is joint work with, among others, Ruchira Datta and Veronika Zarnitsyna of the innate and adaptive immune response subgroup of the MSM working group. For more details see: https://www.science.org/doi/full/10.1126/science.abg3055 *Contents* 0:00 - Introduction J Glazier 2:56 - Coming Up 6:14 - Seminar: Kevin Janes: Stress Testing Complete Kinetic Models of Individualized Enteroviral Infection 33:06 - Seminar: William Waites: Compositional Modelling of Adaptive Immune Response to and Disease Transmission of SARS-CoV-2 51:15 - Q&A Session If you found this video useful, please check out our other videos on computational modeling, infection and immunology: https://youtube.com/playlist?list=PLiEtieOeWbMKh9VcQoinSwODcSZKMTGat Please consider joining our IMAG/MSM WG on Multiscale Modeling and Viral Pandemics: https://www.imagwiki.nibib.nih.gov/content/msm-viral-pandemics-meetings Please also consider joining the Global Alliance for Immune Prediction and Intervention: http://glimprint.org/