Development of IFN-Stimulated Gene Expression from Embryogenesis through Adulthood, with and without Constitutive MDA5 Pathway Activation.

ABSTRACT: Pathogen-associated molecular patterns (e.g., dsRNA) activate expression of IFN-stimulated genes (ISGs), which protect hosts from infection. Although transient ISG upregulation is essential for effective innate immunity, constitutive activation typically causes harmful autoimmunity in mice and humans, often including severe developmental abnormalities. We have shown that transgenic mice expressing a picornavirus RNA-dependent RNA polymerase (RdRP) outside the viral context (RdRP mice) exhibit constitutive, MDA5-dependent, and quantitatively dramatic upregulation of many ISGs, which confers broad viral infection resistance. Remarkably, RdRP mice never develop autoinflammation, interferonopathy, or other discernible abnormalities. In this study, we used RNA sequencing and other methods to an

SUBMITTER: Bankers L 

PROVIDER: S-EPMC7326337 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature