转胶蛋白(Transgelin)促进甲型流感病毒增殖及其负调控I型干扰素产生的机制研究

It has been reported that actin and its related proteins are involved in influenza virus infection process. Through proteomics, we identified that Transgelin may be related to virus infection. Transgelin is an actin-binding protein, studies have found that it is involved in the occurrence of inflammatory responses. Transgelin knockout (Transgelin(-/-)) mice developed enhanced inflammatory responses with higher induction of proinflammatory genes. So we speculate that Transgelin may play an important role in influenza A virus infection and innate immunity response. And our experiments showed that Transgelin could promote the influenza A virus (PR8/H1N1) proliferation and negatively regulate the IFN-β expression. In this study, PR8/H1N1 was used as the model virus to study the mechanism of Transgelin in promoting the influenza A virus proliferation and regulating the natural immune response in cell experiments and mouse experiments. This will not only provide new theoretical basis for understanding the pathogenic mechanism of influenza A virus and host immune response mechanism, but also provide new potential drug targets for prevention and control of influenza A virus infection.

有研究报道肌动蛋白及其相关的多种蛋白参与流感病毒感染过程。本课题组通过前期蛋白质组学鉴定到转胶蛋白(Transgelin)可能与病毒感染有关。Transgelin是肌动蛋白结合蛋白，有研究发现其参与炎症反应的发生；Transgelin基因缺失 (Transgelin(-/-))小鼠炎症反应增强，促炎基因诱导率更高。综上，我们推测Transgelin可能参与甲型流感病毒感染与天然免疫应答过程。因此我们通过实验证实其能够促进甲型流感病毒PR8/H1N1的增殖并能负调控IFN-β的表达。接下来本课题拟以PR8/H1N1为模式病原，通过细胞实验和小鼠实验研究Transgelin在促进甲型流感病毒增殖和调节天然免疫反应方面的作用机制。这不仅能为理解甲型流感病毒致病机制和宿主免疫应答机制提供新的理论依据，还可为防控甲型流感病毒感染提供新的潜在药物靶标。

有研究报道肌动蛋白及其相关的多种蛋白参与流感病毒感染过程。本课题组通过前期蛋白质组学鉴定到转胶蛋白(Transgelin)可能与病毒感染有关。Transgelin是肌动蛋白结合蛋白，有研究发现其参与炎症反应的发生；Transgelin基因缺失 (Transgelin(-/-))小鼠炎症反应增强，促炎基因诱导率更高。因此，本课题研究了Transgelin参与甲型流感病毒感染与天然免疫应答过程中的功能。首先本课题发现Transgelin能够在甲型流感病毒PR8/H1N1感染早期促进该病毒的增殖，且在病毒感染早期Transgelin的表达明显上调；其次，发现Transgelin并不能够影响甲型流感病毒的聚合酶活性，但能够抑制IFN-β的表达；进一步研究发现，Transgelin能够通过与LSM14A相互作用抑制后者信号传到至下游分子RIG-I/VISA，从而抑制病毒感染早期干扰素的产生，从而促进PR8/H1N1感染早期的增殖。本研究丰富了抗病毒天然免疫调节机制相关理论，并为防控甲型流感病毒感染提供新的潜在药物靶标。