Avian metapneumovirus subgroup C induces autophagy through the ATF6 UPR pathway
Avian metapneumovirus subgroup C induces autophagy through the ATF6 UPR pathway
复制标题
禽间质肺病毒 C 亚型通过 ATF6 UPR 途径诱导自噬
DOI：
10.1080/15548627.2017.1356950
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发表时间：
2017-01-01
期刊：
影响因子：
13.3
通讯作者：
Liu, Jue
中科院分区：
文献类型：
--
作者：
Hou, Lei;Wei, Li;Liu, Jue
越来越多的研究表明，巨自噬/自噬在多种病原体的感染过程中起着重要作用。然而，目前尚不清楚在感染禽偏肺病毒(AMPV)的宿主细胞中是否诱导了自噬，如果是，这种自噬是如何发生的。在此，我们报道了AMPV C亚群(AMPV/C)在培养细胞中诱导自噬。我们通过检测经典的自噬特征来证明这种关系，包括自噬的形成，GFP-LC3斑点的存在以及LC3-I到LC3-II的对话。此外，我们使用药物调节因子和针对ATG7或LC3的siRNA来检查自噬在AMPV/C复制中的作用。结果表明，AMPV/C的有效复制需要自噬，并且感染AMPV/C可促进自噬小体成熟并诱导完整的自噬过程。最后，在感染AMPV/C的细胞中，ATF6途径被激活，其中一个组成部分是未折叠蛋白反应(UPR)。ATF6基因敲除可抑制AMPV/C诱导的自噬和病毒复制。综上所述，这些结果不仅表明自噬促进了AMPV/C在培养细胞中的复制，而且揭示了AMPV/C诱导自噬的分子机制依赖于对内质网应激相关UPR通路的调控。
ABSTRACT An increasing number of studies have demonstrated that macroautophagy/autophagy plays an important role in the infectious processes of diverse pathogens. However, it remains unknown whether autophagy is induced in avian metapneumovirus (aMPV)-infected host cells, and, if so, how this occurs. Here, we report that aMPV subgroup C (aMPV/C) induces autophagy in cultured cells. We demonstrated this relationship by detecting classical autophagic features, including the formation of autophagsomes, the presence of GFP-LC3 puncta and the conversation of LC3-I into LC3-II. Also, we used pharmacological regulators and siRNAs targeting ATG7 or LC3 to examine the role of autophagy in aMPV/C replication. The results showed that autophagy is required for efficient replication of aMPV/C. Moreover, infection with aMPV/C promotes autophagosome maturation and induces a complete autophagic process. Finally, the ATF6 pathway, of which one component is the unfolded protein response (UPR), becomes activated in aMPV/C-infected cells. Knockdown of ATF6 inhibited aMPV/C-induced autophagy and viral replication. Collectively, these results not only show that autophagy promotes aMPV/C replication in the cultured cells, but also reveal that the molecular mechanisms underlying aMPV/C-induced autophagy depends on regulation of the ER stress-related UPR pathway.