Interferon-induced antiviral resistance. A mathematical model of regulation of Mx1 protein induction and action.
Influenza A virus and various single-stranded RNA viruses have been reported to be blocked by IFN-stimulated Mx protein. Here we present a mathematical model of regulation of mouse Mx1 protein induction and action under influenza infection. Parameter estimates are derived from published experimental data. Numerical solutions of the model equations completely correspond to experimental data. The model is used to analyse the role of virus- and interferon-mediated expression of Mx1 in maintenance of antiviral state. The study suggests that virus- and IFN-induced Mx1 proteins act on different stages of intracellular ontogenesis of influenza virus and these actions result in different efficacy of cell protection. The model demonstrates that the synergistic action of inteferon and virus in regulation of Mx1 gene expression is the important factor of antiviral resistance. The results of simulation permit to assume that the active form of Mx1 protein is trimer.
Bazhan
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SI
Research Institute of Molecular Biology, State Research Center of Virology and Biotechnology "Vector", 633159 Koltsovo, Novosibirsk Region, Russia.
Belova
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OE
D000818:Animals; D000998:Antiviral Agents / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D019204:GTP-Binding Proteins; D005786:Gene Expression Regulation; D009980:Influenza A virus; D007372:Interferons / Q000502:physiology*; D008099:Liver / Q000821:virology; D051379:Mice; D008822:Mice, Transgenic; D018448:Models, Immunological; D064547:Myxovirus Resistance Proteins; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*
D000998:Antiviral Agents; C579070:Mx1 protein, mouse; D064547:Myxovirus Resistance Proteins; D011506:Proteins; D007372:Interferons; D019204:GTP-Binding Proteins