Zhang Pengfei, Shen Hanqin, Liu Xianhui, Wang Shuangyun, Liu Yanling, Xu Zheng, Song Changxu
College of Animal Science and National Engineering Center for Swine Breeding Industry, South China Agriculture University, Guangzhou, China.
Wen's Foodstuff Group Co. Ltd, Guangdong Enterprise Key Laboratory for Animal Health and Environmental Control, Yunfu, China.
Front Vet Sci. 2020 Dec 17;7:594438. doi: 10.3389/fvets.2020.594438. eCollection 2020.
Porcine circovirus 3 (PCV3) infections cause clinical diseases similar to those seen in porcine circovirus 2 (PCV2) infections. It is unclear whether PCV3 infections can also cause immunosuppression like that seen with PCV2. Here, we report that Cap inhibits DNA-induced IFN-β mRNA transcription and IFN promoter activation. Cap was also found to inhibit cyclic GMP-AMP (cGAMP) synthase (cGAS) binding to interferon-stimulating DNA (ISD). Immunoprecipitation and mass spectrometry were used to identify cellular interaction partners of Cap. Cap interacted with G3BP1 and inhibited the interaction between GTPase-activating protein-(SH3 domain)-binding protein 1 (G3BP1) and cGAS. Furthermore, the destruction of endogenously expressed G3BP1 by siRNA significantly reduced IFN promoter activation, and phosphorylation of tank-binding kinase 1 (TBK1) was induced by ISD. Overexpression of G3BP1 attenuated the inhibition of ISD binding of cGAS by Cap and promoted phosphorylation of TBK1 and IRF3 induced by ISD. Collectively, our results show that the interaction between Cap and G3BP1 prevents cGAS from recognizing DNA, thereby inhibiting the IFN production.
猪圆环病毒3型（PCV3）感染引发的临床疾病与猪圆环病毒2型（PCV2）感染所见的疾病相似。目前尚不清楚PCV3感染是否也会像PCV2那样导致免疫抑制。在此，我们报告Cap抑制DNA诱导的IFN-β mRNA转录和IFN启动子激活。还发现Cap抑制环磷酸鸟苷-腺苷酸（cGAMP）合酶（cGAS）与干扰素刺激DNA（ISD）的结合。采用免疫沉淀和质谱法鉴定Cap的细胞相互作用伙伴。Cap与G3BP1相互作用，并抑制GTP酶激活蛋白（SH3结构域）结合蛋白1（G3BP1）与cGAS之间的相互作用。此外，小干扰RNA（siRNA）对内源表达的G3BP1的破坏显著降低了IFN启动子激活，并且ISD诱导了 Tank结合激酶1（TBK1）的磷酸化。G3BP1的过表达减弱了Cap对cGAS与ISD结合的抑制作用，并促进了ISD诱导的TBK1和干扰素调节因子3（IRF3）的磷酸化。总体而言，我们的结果表明Cap与G3BP1之间的相互作用阻止了cGAS识别DNA，从而抑制了IFN的产生。
