While there is conflicting evidence for the role of IFI16 in IFN-β responses to foreign DNA challenge, multiple lines of investigation indicate that this DNA sensor contributes to IFN-β and ISG expression following viral infection (Orzalli et al., 2012; Jakobsen et al., 2013; Ansari et al., 2015; Diner et al., 2015; Ma F. et al., 2015; Li et al., 2016; Zhang D. et al., 2016; Jønsson et al., 2017; Lum et al., 2019; Yang et al., 2020). This evidence concerns the gene IFNB1 and viral infectious disease.