Comparative computational modeling of the bat and human immune response to viral infection with the Comparative Biology Immune Agent Based Model

Abstract

Given the impact of pandemics due to viruses of bat origin there is increasing interest in comparative investigation into the differences between bat and human immune responses. The practice of comparative biology can be enhanced by computational methods used for dynamic knowledge representation to visualize and interrogate the putative differences between the two systems. We present an agent-based model that encompasses and bridges the differences between bat and human responses to viral infection: the Comparative Biology Immune Agent-based Model, or CBIABM. The CBIABM examines differences in innate immune mechanisms between bats and humans, specifically regarding inflammasome activity and Type 1 Interferon dynamics, in terms of tolerance to viral infection. Simulation experiments with the CBIABM demonstrate the efficacy of bat-related features in conferring viral tolerance and also suggest a crucial role for endothelial inflammasome activity as a mechanism for bat systemic viral tolerance and affecting the severity of disease in human viral infections. We hope that this initial study will inspire additional comparative modeling projects to link, compare, and contrast immunological functions shared across different species, and in so doing, provide insight and aid in the preparation for future viral pandemics of zoonotic origin.