Individual ISGs have measurable phenotypes in vivo.
•
ISGs control viral pathogenesis through a variety of mechanisms.
•
ISG effects in vivo are often virus-specific, cell-specific, and tissue-specific.
Interferon-stimulated genes (ISGs) are critical for controlling virus infections. As new antiviral ISGs continue to be identified and characterized, their roles in viral pathogenesis are also being explored in more detail. Our current understanding of how ISGs impact viral pathogenesis comes largely from studies in knockout mice, with isolated examples from human clinical data. This review outlines recent developments on the contributions of various ISGs to viral disease outcomes in vivo.