Newcastle disease virus NP and P proteins induce autophagy via the endoplasmic reticulum stress-related unfolded protein response.
Newcastle disease virus NP and P proteins induce autophagy via the endoplasmic reticulum stress-related unfolded protein response.
复制标题
新城疫病毒 NP 和 P 蛋白通过内质网应激相关未折叠蛋白反应诱导自噬
DOI：
10.1038/srep24721
复制
发表时间：
2016-04-21
影响因子：
4.6
通讯作者：
Ding C
中科院分区：
文献类型：
--
作者：
Cheng JH;Sun YJ;Zhang FQ;Zhang XR;Qiu XS;Yu LP;Wu YT;Ding C
纽卡斯尔病病毒（NDV）可在人类肿瘤细胞中复制并引发自噬。我们先前的研究证实了自噬在NDV感染中的关键作用。在这里，我们研究了NDV结构蛋白通过内质网（ER）应激相关的未折叠蛋白反应（UPR）途径诱导自噬的作用。NDV核衣壳蛋白（NP）或磷蛋白（P）的异位表达足以诱导自噬。NP或P的表达也改变了ER的稳态。PERK和ATF6途径，但不是XBP1途径，所有这些都是UPR的组成部分，在NDV感染和NP或P转染的细胞中被激活。敲低PERK或ATF6抑制NDV诱导的自噬，并降低NDV复制的程度。总的来说，这些数据不仅表明NDV NP和P蛋白在自噬中的作用，而且还通过激活ER应激相关的UPR途径对NDV诱导的自噬机制提供了新的见解。
Newcastle disease virus (NDV) can replicate and trigger autophagy in human tumor cells. Our previous study confirmed the critical role of autophagy in NDV infection. Here we studied the role of NDV structural proteins in the induction of autophagy through endoplasmic reticulum (ER) stress-related unfolded protein response (UPR) pathways. Ectopic expression of the NDV nucleocapsid protein (NP) or phosphoprotein (P) was sufficient to induce autophagy. NP or P expression also altered ER homeostasis. The PERK and ATF6 pathways, but not the XBP1 pathway, all of which are components of the UPR, were activated in both NDV-infected and NP or P-transfected cells. Knockdown of PERK or ATF6 inhibited NDV-induced autophagy and reduced the extent of NDV replication. Collectively, these data suggest not only roles for the NDV NP and P proteins in autophagy, but also offer new insights into the mechanisms of NDV-induced autophagy through activation of the ER stress-related UPR pathway.