Mortalin restricts porcine epidemic diarrhea virus entry by downregulating clathrin-mediated endocytosis
Mortalin restricts porcine epidemic diarrhea virus entry by downregulating clathrin-mediated endocytosis
复制标题
Mortalin 通过下调网格蛋白介导的内吞作用来限制猪流行性腹泻病毒的进入
DOI：
10.1016/j.vetmic.2019.108455
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发表时间：
2019-12-01
影响因子：
3.3
通讯作者：
Li, Bin
中科院分区：
文献类型：
--
作者：
Fan, Baochao;Zhu, Lin;Li, Bin
网状蛋白介导的内吞作用是多种病毒入侵细胞的一种机制。Mortalin蛋白参与多种细胞功能，并在病毒感染中发挥作用。在本研究中，我们发现mortalin通过限制病毒进入而显著抑制猪流行性腹泻病毒(PEDV)的复制。从机制上讲，mortalin的羧基末端与clathrin Heavy Chain(Cltc)之间存在生化相互作用，mortalin可通过蛋白酶体途径诱导Cltc降解，从而抑制clathrin介导的PEDV内吞进入宿主细胞。此外，mortalin表达的人为改变影响了转铁蛋白的细胞进入，进一步证实了上述结果。最后，我们证实这种宿主安装的抗病毒机制广泛适用于其他病毒，如水疱性口炎病毒(VSV)、轮状病毒(RV)和传染性胃肠炎病毒(TGEV)，它们使用相同的网状蛋白介导的内吞入胞。这些结果揭示了mortalin抑制内吞作用的新功能，并为治疗PEDV感染提供了一种新的策略。
Clathrin-mediated endocytosis is a mechanism used for the invasion of cells by a variety of viruses. Mortalin protein is involved in a variety of cellular functions and plays a role in viral infection. In this study, we found that mortalin significantly inhibited the replication of porcine epidemic diarrhea virus (PEDV) through restricting virus entry. Mechanistically, a biochemical interaction between the carboxyl terminus of mortalin and clathrin heavy chain (CLTC) was been found, and mortalin could induce CLTC degradation through the proteasomal pathway, thereby inhibiting the clathrin-mediated endocytosis of PEDV into host cells. In addition, artificial changes in mortalin expression affected the cell entry of transferrin, further confirming the above results. Finally, we confirmed that this host-mounted antiviral mechanism was broadly applicable to other viruses, such as vesicular stomatitis virus (VSV), rotavirus (RV), and transmissible gastroenteritis virus (TGEV), which use the same clathrin-mediated endocytic to entry. These results reveal a new function of mortalin in inhibiting endocytosis, and provide a novel strategy for treating PEDV infections.