A Systems and Treatment Perspective of Models of Influenza Virus-Induced Host Responses

Abstract

Abstract:Severe influenza infections are often characterized as having unique host responses (e.g., early, severe hypercytokinemia). Neuraminidase inhibitors can be effective in controlling the severe symptoms of influenza but are often not administered until late in the infection. Several studies suggest that immune modulation may offer protection to high risk groups. Here, we review the current state of mathematical models of influenza-induced host responses. Selecting three models with conserved immune response components, we determine if the immune system components which most affect virus replication when perturbed are conserved across the models. We also test each model's response to a pre-induction of interferon before the virus is administered. We find that each model emphasizes the importance of controlling the infected cell population to control viral replication. Moreover, our work shows that the structure of current models does not allow for significant responses to increased interferon concentrations. These results suggest that the current library of available published models of influenza infection does not adequately represent the complex interactions of the virus, interferon, and other aspects of the immune response. Specifically, the method used to model virus-resistant cells may need to be adapted in future work to more realistically represent the immune response to viral infection.

Mathematical Modeling Finds Disparate Interferon Production Rates Drive Strain-Specific Immunodynamics during Deadly Influenza Infection

“…Dynamic mathematical models have been used to better understand the mechanisms driving in vitro and in vivo immunodynamics observed during influenza infection (see [ 13 , 14 ] for reviews of some relevant models). To date, most mathematical models of influenza infection consist of ordinary differential equations (ODEs) that systematically link virus replication and the availability of host target cells (cells that can be infected) to intracellular immune signaling (interferon responses) and/or immune cell activity.…”

Compartmental Model Suggests Importance of Innate Immune Response to COVID-19 Infection in Rhesus Macaques

“…Here we present an ordinary differential equation (ODE) model of the inflammatory response to COVID-19 infection. Mathematical modeling has long been used to describe the immune response to lung infection (Baccam et al 2006;Hernandez-Vargas et al 2014;Miao et al 2011;Mochan-Keef et al 2015;Mochan et al 2018Mochan et al , 2014Price et al 2015;Saenz et al 2010;Smith et al 2011). Our model focuses on the importance of the inflammatory response to viral infection, using feedback from the pro-inflammatory mediators to suppress viral growth and induce incidental damage to the epithelium.…”