天然免疫信号蛋白在仙台病毒感染过程中聚集于应激颗粒

Innate Immune Signaling Protein Aggregates to Sendai Virus Induced Stress Granules

病毒感染通常导致细胞中蛋白翻译关闭,形成应激颗粒(SG)。已有报道表明仙台病毒(Se V)C蛋白参与抑制SG的形成,然而,SG在Se V感染过程中的作用尚不清楚。为探讨SG在Se V感染过程中发挥的作用,本研究利用Se V感染He La细胞,以间接免疫荧光检测SG核心蛋白G3BP1的聚集和天然免疫信号蛋白的亚细胞定位情况。结果显示:一部分SEV感染的细胞诱导G3BP1聚集为点状颗粒,形成SG;病毒RNA感受器RIG-I和MDA5,天然免疫信号通路相关激酶TBK1、IKKε、TAK1、IKKβ,RNA解旋酶DDX3、泛素连接酶和去泛素化酶A20和CYLD向SG迁移并发生点状聚集。以上结果表明,SEV感染过程中,SG招募天然免疫翻译信号蛋白,进一步证实SG参与了宿主的抗病毒天然免疫应答,揭示细胞压力应激和天然免疫应答之间存在交叉作用。

Stress granule(SG) is a dense granular polymer formed in cytoplasm in response to stress, including virus infection. It has been reported that Sendai virus(SeV) C protein inhibits the formation of SG during virus infection. However, the role of SG in response to SeV infection is unclear. To elucidate the function of SG during SeV infection, we studied the formation of SG and the subcellular location of innate immune signaling proteins during SeV infection. We found that SeV triggered the formation of SG in a proportion of infected HeLa cells. The virus RNA sensors MDA5 and RIG-I, innate immune signaling transmitting kinase TBK1, IKKε, TAK1, and IKKβ, helicase DDX3, ubiquitin ligase and deubiquitinase A20 and CYLD aggregate to the SeV-induced SGs as evidenced by indirect immunofl uorescence. Therefore, we speculated that SGs were involved in innate immune response during SeV infection. This study added evidence that SG indeed played a role in host anti-viral response and revealed the crosstalks between integral stress response and innate immune response.