title: Model of influenza A virus infection: dynamics of viral antagonism and innate immune response.
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.
authors.affiliation: Department of Neurology and Center for Translational Systems Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States.
authors.forename: M
authors.initials: M
authors.lastname: Fribourg
authors.affiliation: Department of Neurology and Center for Translational Systems Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States.
authors.forename: B
authors.initials: B
authors.lastname: Hartmann
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States.
authors.forename: M
authors.initials: M
authors.lastname: Schmolke
authors.affiliation: Department of Neurology and Center for Translational Systems Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States.
authors.forename: N
authors.initials: N
authors.lastname: Marjanovic
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States.
authors.forename: R A
authors.initials: RA
authors.lastname: Albrecht
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States.
authors.forename: A
authors.initials: A
authors.lastname: García-Sastre
authors.affiliation: Department of Neurology and Center for Translational Systems Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States.
authors.forename: S C
authors.initials: SC
authors.lastname: Sealfon
authors.affiliation: Department of Physics, Ohio State University, Columbus, OH 43210, United States.
authors.forename: C
authors.initials: C
authors.lastname: Jayaprakash
authors.affiliation: Department of Neurology and Center for Translational Systems Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States. Electronic address: fernand.hayot@mssm.edu.
authors.forename: F
authors.initials: F
authors.lastname: Hayot
mesh_terms: D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D015870:Gene Expression / Q000276:immunology; D054884:Host-Pathogen Interactions; D006801:Humans; D057131:Immune Evasion; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000145:classification / Q000276:immunology* / Q000472:pathogenicity; D007251:Influenza, Human / Q000235:genetics / Q000276:immunology* / Q000821:virology; D016899:Interferon-beta / Q000096:biosynthesis; D018448:Models, Immunological; D017361:Viral Nonstructural Proteins / Q000502:physiology
chemical_list: C085820:INS1 protein, influenza virus; D017361:Viral Nonstructural Proteins; D016899:Interferon-beta
keywords: Immunology; Interferon; NS1; ODE model