Yuan Peipei, Dong Lanlan, Cheng Qingqing, Wang Shuang, Li Zhi, Sun Yan, Han Song, Yin Jun, Peng Biwen, He Xiaohua, Liu Wanhong
Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, No. 185, Donghu Road, Wuchang District, Wuhan, 430071, China.
Hubei Provincial Key Laboratory of Developmentally Originated Disease, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, China.
Retrovirology. 2017 Mar 7;14(1):16. doi: 10.1186/s12977-017-0341-x.
Prototype foamy virus (PFV) is a member of the Spumaretrovirinae subfamily of retroviruses, which maintains lifelong latent infection while being nonpathogenic to their natural hosts. Autophagy is a cell-programmed mechanism that plays a pivotal role in controlling homeostasis and defense against exotic pathogens. However, whether autophagy is the mechanism for host defense in PFV infection has not been investigated.
Our results revealed that PFV infection induced the accumulation of autophagosomes and triggered complete autophagic flux in BHK-21 cells. PFV infection also altered endoplasmic reticulum (ER) homeostasis. The PERK, IRE1 and ATF6 pathways, all of which are components of the ER stress-related unfolded protein response (UPR), were activated in PFV-infected cells. In addition, accelerating autophagy suppressed PFV replication, and inhibition of autophagy promoted viral replication.
Our data indicate that PFV infection can induce complete autophagy through activating the ER stress-related UPR pathway in BHK-21 cells. In turn, autophagy negatively regulates PFV replication.
原型泡沫病毒（PFV）是逆转录病毒泡沫逆转录病毒亚科的成员，它能维持终身潜伏感染，同时对其自然宿主无致病性。自噬是一种细胞程序性机制，在控制体内平衡和抵御外来病原体方面起着关键作用。然而，自噬是否是PFV感染中宿主防御的机制尚未得到研究。
我们的结果显示，PFV感染诱导了自噬体的积累，并在BHK-21细胞中触发了完整的自噬流。PFV感染还改变了内质网（ER）的稳态。PERK、IRE1和ATF6途径，这些都是内质网应激相关未折叠蛋白反应（UPR）的组成部分，在PFV感染的细胞中被激活。此外，加速自噬抑制了PFV复制，而抑制自噬则促进了病毒复制。
我们的数据表明，PFV感染可通过激活BHK-21细胞中内质网应激相关的UPR途径诱导完整的自噬。反过来，自噬对PFV复制起负调节作用。
