Cells sensing infection produce Type I interferons (IFN-I) to stimulate Interferon Stimulated Genes (ISGs) that confer resistance to viruses. During lympho-hematogenous spread of the mouse pathogen ectromelia virus (ECTV), the adaptor STING and the transcription factor IRF7 are required for IFN-I and ISG induction and resistance to ECTV. However, it is unknown which cells sense ECTV and which pathogen recognition receptor (PRR) upstream of STING is required for IFN-I and ISG induction. We found that cyclic-GMP-AMP (cGAMP) synthase (cGAS), a DNA-sensing PRR, is required in bone marrow-derived (BMD) but not in other cells for IFN-I and ISG induction and for resistance to lethal mousepox. Also, local administration of cGAMP, the product of cGAS that activates STING, rescues cGAS but not IRF7 or IFN-I receptor deficient mice from mousepox. Thus, sensing of infection by BMD cells via cGAS and IRF7 is critical for resistance to a lethal viral disease in a natural host.

中文翻译：

---

对念珠菌病毒感染的抵抗力要求骨髓来源的细胞中具有cGAS，而cGAMP治疗可以绕过它。

感测感染的细胞产生I型干扰素（IFN-I），以刺激对病毒具有抗性的干扰素刺激基因（ISG）。在小鼠病原菌埃克氏菌病毒（ECTV）的淋巴血细胞性扩散过程中，需要使用衔接子STING和转录因子IRF7来诱导IFN-1和ISG以及对ECTV的抵抗力。但是，尚不清楚哪些细胞能感应ECTV，以及在STING上游需要哪些病原体识别受体（PRR）来诱导IFN-1和ISG。我们发现，在骨髓来源的（BMD）中需要DNA感测PRR的环状GMP-AMP（cGAMP）合酶（cGAS），但在其他细胞中则不需要IFN-I和ISG诱导以及对致命的鼠痘的抗性。同样，局部激活cGAMP的产物cGAMP可以激活STING，可以从鼠痘中拯救cGAS，但不能拯救IRF7或IFN-I受体缺陷的小鼠。因此，