Contributors
Kevin Janes Univ. of Virginia, Title: Stress testing complete kinetic models of individualized enteroviral infection
William Waites, Univ. of Strathclyde, Title: Compositional modelling of adaptive immune response to and disease transmission of SARS-CoV-2
William Waites, Univ. of Strathclyde, Title: Compositional modelling of adaptive immune response to and disease transmission of SARS-CoV-2
Institution/ Affiliation
Kevin Janes Univ. of Virginia
William Waites, Univ. of Strathclyde
William Waites, Univ. of Strathclyde
Presentation Details (date, conference, etc.)
February 10, 2022, IMAG/MSM WG on Multiscale Modeling and Viral Pandemics
- Kevin Janes Univ. of Virginia, Title: Stress testing complete kinetic models of individualized enteroviral infection. Abstract: 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. 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. YouTube, Slides and relevant papers (1, 2).
- William Waites, Univ. of Strathclyde, Title: Compositional modelling of adaptive immune response to and disease transmission of SARS-CoV-2 Abstract: 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. YouTube and Slides.