Model of influenza A virus infection: Dynamics of viral antagonism and innate immune response

• Published in: Journal of theoretical biology 2014-06, Vol.351, p.47-57
• Main Authors: Fribourg, M., Hartmann, B., Schmolke, M., Marjanovic, N., Albrecht, R.A., García-Sastre, A., Sealfon, S.C., Jayaprakash, C., Hayot, F.
• Format: Article
• Language: English
• Subjects: Dendritic Cells - immunology; Dendritic Cells - virology; Gene Expression - immunology; Host-Pathogen Interactions; Humans; Immune Evasion; Immunity, Innate - genetics; Immunity, Innate - immunology; Immunology; Influenza A virus; Influenza A Virus, H1N1 Subtype - classification; Influenza A Virus, H1N1 Subtype - immunology; Influenza A Virus, H1N1 Subtype - pathogenicity; Influenza, Human - genetics; Influenza, Human - immunology; Influenza, Human - virology; Interferon; Interferon-beta - biosynthesis; Models, Immunological; NS1; ODE model; Viral Nonstructural Proteins - physiology
• ISSN: 0022-5193; 1095-8541
• DOI: 10.1016/j.jtbi.2014.02.029

Viral antagonism of host responses is an essential component of virus pathogenicity. The study of the interplay between immune response and viral antagonism is challenging due to the involvement of many processes acting at multiple time scales. Here we develop an ordinary differential equation model to investigate the early, experimentally measured, responses of human monocyte-derived dendritic cells to infection by two H1N1 influenza A viruses of different clinical outcomes: pandemic A/California/4/2009 and seasonal A/New Caledonia/20/1999. Our results reveal how the strength of virus antagonism, and the time scale over which it acts to thwart the innate immune response, differs significantly between the two viruses, as is made clear by their impact on the temporal behavior of a number of measured genes. The model thus sheds light on the mechanisms that underlie the variability of innate immune responses to different H1N1 viruses. •We study two influenza A H1N1 viral strains with different clinical outcomes.•We model the dynamics of the interplay between the viral antagonism and the innate immune response.•We extract the dynamic features of viral antagonism and innate immune response from time course gene expression measurements for a set of selected genes.•We find that the strength and time scale of action of viral antagonism is significantly different between the two viruses.