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

J Theor Biol. 2014 Jun 21:351:47-57. doi: 10.1016/j.jtbi.2014.02.029. Epub 2014 Mar 2.

Abstract

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.

Keywords: Immunology; Interferon; NS1; ODE model.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Dendritic Cells / immunology
  • Dendritic Cells / virology
  • Gene Expression / immunology
  • Host-Pathogen Interactions
  • Humans
  • Immune Evasion
  • Immunity, Innate / genetics
  • Immunity, Innate / immunology
  • 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-beta / biosynthesis
  • Models, Immunological*
  • Viral Nonstructural Proteins / physiology

Substances

  • INS1 protein, influenza virus
  • Viral Nonstructural Proteins
  • Interferon-beta