Dynamically Linking Influenza Virus Infection Kinetics, Lung Injury, Inflammation, and Disease Severity

Myers, Margaret A.; Smith, Amanda P.; Lane, Lindey C.; Moquin, David J.; Aogo, Rosemary; Woolard, Stacie; Thomas, Paul G.; Vogel, Peter; Smith, Amber M.

Influenza viruses cause a significant amount of morbidity and mortality. Understanding host immune control efficacy and how different factors influence lung injury and disease severity are critical. Here, we established dynamical connections between viral loads, infected cells, CD8+ T cell-mediated clearance, lung injury, inflammation, and disease severity using an integrative model-experiment exchange. The model was validated through CD8 depletion and whole lung histomorphometry, which showed that the infected area matched the model-predicted infected cell dynamics and that the resolved area paralleled the relative CD8 dynamics. Inflammation could further be predicted by the infected cell dynamics, and additional analyses revealed nonlinear relations between lung injury, inflammation, and disease severity. These links between important pathogen kinetics and host pathology enhance our ability to forecast disease progression, potential complications, and therapeutic efficacy.