Modelling molecular differences in the innate immune system responses of chickens and ducks to highly pathogenic avian influenza virus

Abstract

Highly pathogenic avian influenza virus (HPAIV) presents a global threat to chicken livestock; chickens infected by HPAIV tend to show severe symptoms and high mortality rates. In 2022, the largest recorded outbreak of HPAIV in Europe resulted in millions of chickens being culled in the UK alone to try to prevent further spread. Unlike chickens, mallard ducks show reduced symptom severity and lower mortality rates to HPAIV infection. Research into the immune system responses of these two species shows they differ in their molecular outputs: chickens produce a pro-inflammatory response; mallards produce an anti-viral response. These differences in immune responses are thought to be in part due to chickens missing pattern recognition receptor retinoic acid-inducible gene-I (RIG-I). This project aimed to model the innate immune systems of chickens and mallard ducks to an abstracted molecular level. A literature search was conducted, and the immune systems were modelled in NetLogo as an avian innate immune response agent-based model (AIIRABM). The AIIRABM enabled examination of the relative importance of molecular differences between the chicken and mallard duck innate immune systems and produced similar differences in chicken and mallard duck molecular outputs to those observed in vitro and in vivo. Simulation experiments with the AIIRABM supported the molecular difference RIG-I as key in causing the differences in the chicken and mallard duck innate immune responses to HPAIV. The AIIRABM will be used in further research on the chicken and mallard duck immune responses to HPAIV as the baseline in an iterative modelling cycle.