Transcriptional regulation of numerous interferon-regulated genes, including Toll-like receptor 3 (Tlr3), which encodes an innate immune sensor of viral double-stranded RNA, depends on the interferon regulatory factor 1 (IRF1) and IRF2 transcription factors. We detected specific abrogation of macrophage responses to polyinosinic-polycytidylic acid (poly(I:C)) resulting from three independent N-ethyl-N-nitrosourea–induced mutations in host cell factor C2 (Hcfc2). Hcfc2 mutations compromised survival during influenza virus and herpes simplex virus 1 infections. HCFC2 promoted the binding of IRF1 and IRF2 to the Tlr3 promoter, without which inflammatory cytokine and type I IFN responses to the double-stranded RNA analogue poly(I:C) are reduced in mouse macrophages. HCFC2 was also necessary for the transcription of a large subset of other IRF2-dependent interferon-regulated genes. Deleterious mutations of Hcfc2 may therefore increase susceptibility to diverse infectious diseases.

多种干扰素调节基因的转录调节，包括编码病毒双链RNA的先天免疫传感器的Toll样受体3（Tlr3），取决于干扰素调节因子1（IRF1）和IRF2转录因子。我们检测到了巨噬细胞对多肌苷酸-聚胞苷酸（poly（I：C））的特异性消除，这是由宿主细胞因子C2（Hcfc2）的三个独立的N-乙基-N-亚硝基脲诱导的突变导致的。Hcfc2突变损害了流感病毒和单纯疱疹病毒1感染期间的生存。HCFC2促进了IRF1和IRF2与Tlr3的结合启动子，在小鼠巨噬细胞中，对双链RNA类似物poly（I：C）的炎性细胞因子和I型IFN反应降低。HCFC2对于转录大量其他依赖IRF2的干扰素调节基因也是必需的。因此，Hcfc2的有害突变可能会增加对各种传染病的敏感性。