Model Description:

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.

ModelInfluenzaA
Figure 1: Schematic of the model considered, where the points of application of NS1 antagonism are highlighted. There are three compartments, medium, cytoplasm and nucleus, and positive feedback loops associated with IFNβ, IFNα, and TNFα.

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.

References:

  1. M. Fribourg, et al.: Model of influenza A virus infection: Dynamics of viral antagonism and innate immune response. Journal of Theoretical Biology, Volume 351, 21 June 2014, Pages 47–57
  2. H1N1 influenza A virus - NC/99 [SBML]
  3. H1N1 influenza A virus - Cal/09 [SBML]