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Upon infection, the IFN\u2010I are rapidly secreted and induce a wide range of effects that not only act upon innate immune cells but also modulate the adaptive immune system. While IFN\u2010I and many IFN stimulated genes are well\u2010known for their protective antiviral role, recent studies have associated them with potential pathogenic functions. In this review, we summarize the current knowledge regarding the complex effects of human IFN\u2010I responses in respiratory as well as reemerging flavivirus infections of public health significance and the molecular mechanisms by which viral proteins antagonize the establishment of an antiviral host defense. Antiviral effects and immune modulation of IFN\u2010stimulated genes is discussed in resisting and controlling pathogens. 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