The invasion of tobacco mosaic virus RNA induces endoplasmic reticulum stress-related autophagy in HeLa cells

Li, Li; Wang, Li; Xiao, Ruijing; Zhu, Guoguo; Li, Yan; Liu, Changxuan; Yang, Ru; Tang, Zhiqing; Li, Jie; Huang, Wei; Chen, Lang; Zheng, Xiaoling; He, Yuling; Tan, Jinquan

Some recent studies have demonstrated that the occurrence of autophagy is very closely associated with ERS [46] [47] [48] [49] . Ogata et al. [24] found that the autophagy process was activated as a novel signalling pathway in response to ERS. Although we have strong morphological evidence, we still require evidence at the molecular level to further uncover the direct relationships among TMV, ERS and autophagy. We found that the translation of TMV-RNA induced ERS, and this effect was verified by the accumulation of GRP78 in the ER. As an ER chaperone, GRP78 not only binds to unfolded proteins but also regulates the activation of ERS transducers, such as IRE1, PERK and ATF6. With the accumulation of TMV proteins, GRP78 would inevitably interact with the viral proteins as well as activate ERS signal transduction proteins, causing other cellular responses, such as the UPR and autophagy. Li showed that the UPR regulator and ER chaperone, GRP78/BiP, was required for stressinduced autophagy [50] . Whether GRP78 was also required in our study may be one way to verify ERS-induced autophagy.