The epidermal growth factor receptor regulates cofilin activity and promotes transmissible gastroenteritis virus entry into intestinal epithelial cells.
The epidermal growth factor receptor regulates cofilin activity and promotes transmissible gastroenteritis virus entry into intestinal epithelial cells.
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表皮生长因子受体调节丝切蛋白活性并促进传染性胃肠炎病毒进入肠上皮细胞
DOI：
10.18632/oncotarget.7723
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发表时间：
2016-03-15
期刊：
影响因子：
--
通讯作者：
Yang Q
中科院分区：
文献类型：
--
作者：
Hu W;Zhu L;Yang X;Lin J;Yang Q
传染性胃肠炎病毒（TGEV）是一种冠状病毒，可引起新生仔猪严重腹泻和高死亡率。猪传染性胃肠炎病毒（TGEV）感染的靶细胞是猪小肠上皮细胞，但TGEV破坏肌动蛋白细胞骨架并侵入宿主上皮细胞的机制尚不清楚。我们不仅发现TGEV感染刺激F-actin聚集在细胞膜上，而且F-actin的破坏也抑制了TGEV的进入。Cofilin参与F-肌动蛋白重组和TGEV进入。TGEV刺突蛋白能够与EGFR结合，激活下游磷酸肌醇-3激酶（PI 3 K），然后通过Rac 1/Cdc 42 GTP酶引起cofilin的磷酸化和F-肌动蛋白聚合。EGFR和PI 3 K的抑制减少了TGEV的进入。EGFR也是参与F-肌动蛋白重组的丝裂原活化蛋白激酶（MAPK）信号通路的上游激活剂。此外，脂筏作为EGFR相关信号级联的信号平台，与TGEV的粘附相关。这些结果为TGEV的致病机制提供了有价值的数据，并可能导致开发新的控制TGEV的方法。
Transmissible gastroenteritis virus (TGEV), a coronavirus, causes severe diarrhea and high mortality in newborn piglets. The porcine intestinal epithelium is the target of TGEV infection, but the mechanisms that TGEV disrupts the actin cytoskeleton and invades the host epithelium remain largely unknown. We not only found that TGEV infection stimulates F-actin to gather at the cell membrane but the disruption of F-actin inhibits TGEV entry as well. Cofilin is involved in F-actin reorganization and TGEV entry. The TGEV spike protein is capable of binding with EGFR, activating the downstream phosphoinositide-3 kinase (PI3K), then causing the phosphorylation of cofilin and F-actin polymerization via Rac1/Cdc42 GTPases. Inhibition of EGFR and PI3K decreases the entry of TGEV. EGFR is also the upstream activator of mitogen-activated protein kinase (MAPK) signaling pathways that is involved in F-actin reorganization. Additionally, lipid rafts act as signal platforms for the EGFR-associated signaling cascade and correlate with the adhesion of TGEV. In conlusion, these results provide valuable data of the mechanisms which are responsible for the TGEV pathogenesis and may lead to the development of new methods about controlling TGEV.