Host-pathogen kinetics during influenza infection and coinfection: insights from predictive modeling

Influenza virus infections are a leading cause of morbidity and mortality worldwide. This is due in part to the continual emergence of new viral variants and to synergistic interactions with other viruses and bacteria. There is a lack of understanding about how host responses work to control the infection and how other pathogens capitalize on the altered immune state. The complexity of multi-pathogen infections makes dissecting contributing mechanisms, which may be non-linear and occur on different time scales, challenging. Fortunately, mathematical models have been able to uncover infection control mechanisms, establish regulatory feedbacks, connect mechanisms across time scales, and determine the processes that dictate different disease outcomes. These models have tested existing hypotheses and generated new hypotheses, some of which have been subsequently tested and validated in the laboratory. They have been particularly a key in studying influenza-bacteria coinfections and will be undoubtedly be useful in examining the interplay between influenza virus and other viruses. Here, I review recent advances in modeling influenza-related infections, the novel biological insight that has been gained through modeling, the importance of model-driven experimental design, and future directions of the field.