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.
Highlights
Influenza A virus (IAV) leads to acute respiratory disease and significant morbidity and mortality around the world each year; the World Health Organization estimates three to five million cases of severe illness and 300,000–650,000 deaths worldwide every year are caused by IAV [1]
Interferon can lead to enhanced infected cell clearance by stimulating the activation of natural killer cells, which are not explicitly represented in the model
We did not use this artificial delay in infected cell clearance, as a delay equation would not be consistent with the other two models presented in this review
Summary
Influenza A virus (IAV) leads to acute respiratory disease and significant morbidity and mortality around the world each year; the World Health Organization estimates three to five million cases of severe illness and 300,000–650,000 deaths worldwide every year are caused by IAV [1]. The 1918 Spanish influenza pandemic is estimated to have been responsible for the death of 2% of the world’s population between 1918 and 1920 [2]. H5N1 infections have demonstrated the ability to cause severe disease in humans, including symptoms such as fever, respiratory symptoms, lymphopenia, and cytokine storm (hypercytokinemia) [5,6,7]. Cytokine storm occurs when the host experiences out-of-control pro-inflammatory responses and insufficient anti-inflammatory responses to infection
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
