IFIH1 (Interferon-induced helicase C domain-containing protein 1) is an innate immune receptor that acts as a cytoplasmic sensor of viral nucleic acids and plays a major role in sensing viral infection and in the activation of a cascade of antiviral responses including the induction of type I interferons and proinflammatory cytokines. It is responsible for detecting the Picornaviridae family members such as encephalomyocarditis virus (EMCV) and mengo encephalomyocarditis virus (ENMG), and it can also detect other viruses such as dengue virus (DENV), west Nile virus (WNV), and reovirus. It is further involved in antiviral signaling in response to viruses containing a dsDNA genome, such as vaccinia virus. IFIH1 plays an important role in amplifying innate immune signaling through recognition of RNA metabolites that are produced during virus infection by ribonuclease L (RNase L). It may play an important role in enhancing natural killer cell function and may be involved in growth inhibition and apoptosis in several tumor cell lines. In immunohistochemistry, IFIH1 has cytoplasmic and nuclear positivity in most tissues throughout the body (nuclear localization is thought to occur during apoptosis). References: The UniProt Consortium. Nucleic Acids Res. 47: D506-515 (2019); Nucleic Acids Res. 2016 Jan 4;44(D1):D733-45, PMID:26553804;