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The type-I interferon (IFN) response is one of the fundamental mechanisms of immune defense against coronavirus infections, including the highly pathogenic SARS coronavirus. Plasmacytoid dendritic cells (pDC) are the major cell population for the type-I IFN mediated control of the initial phase of virus replication. In this study we develop an integrative mathematical model for the antiviral interferon response using the data coming from the murine coronavirus (mouse hepatitis virus, MHV) experimental system. We apply a building block (bottom-up) approach to setting up the mathematical model by decomposing the complex system dynamics into a set of ‘elementary’ processes (e.g. cell persistence, pDC infection) for which a data-consistent quantitative description is identified via maximum likelihood parameter estimation. Information-theoretic criteria are applied to evaluate the models in the context of available data sets. By sensitivity analysis to parameter variations the model is used to understand the ‘numbers game’ for the virus induced type-I IFN response and evaluate the protective capacity of pDC-derived type I IFN.