title: The invasion of tobacco mosaic virus RNA induces endoplasmic reticulum stress-related autophagy in HeLa cells.
abstract: The ability of human cells to defend against viruses originating from distant species has long been ignored. Owing to the pressure of natural evolution and human exploration, some of these viruses may be able to invade human beings. If their 'fresh' host had no defences, the viruses could cause a serious pandemic, as seen with HIV, SARS (severe acute respiratory syndrome) and avian influenza virus that originated from chimpanzees, the common palm civet and birds, respectively. It is unknown whether the human immune system could tolerate invasion with a plant virus. To model such an alien virus invasion, we chose TMV (tobacco mosaic virus) and used human epithelial carcinoma cells (HeLa cells) as its 'fresh' host. We established a reliable system for transfecting TMV-RNA into HeLa cells and found that TMV-RNA triggered autophagy in HeLa cells as shown by the appearance of autophagic vacuoles, the conversion of LC3-I (light chain protein 3-I) to LC3-II, the up-regulated expression of Beclin1 and the accumulation of TMV protein on autophagosomal membranes. We observed suspected TMV virions in HeLa cells by TEM (transmission electron microscopy). Furthermore, we found that TMV-RNA was translated into CP (coat protein) in the ER (endoplasmic reticulum) and that TMV-positive RNA translocated from the cytoplasm to the nucleolus. Finally, we detected greatly increased expression of GRP78 (78 kDa glucose-regulated protein), a typical marker of ERS (ER stress) and found that the formation of autophagosomes was closely related to the expanded ER membrane. Taken together, our data indicate that HeLa cells used ERS and ERS-related autophagy to defend against TMV-RNA.
authors: Laboratory of Allergy and Clinical Immunology, Department of Immunology, Institute of Allergy and Immune-related Diseases, Centre for Medical Research, Wuhan University School of Medicine, Wuhan, People's Republic of China.
authors: Li
authors: L
authors: Li
authors: Li
authors: L
authors: Wang
authors: Ruijing
authors: R
authors: Xiao
authors: Guoguo
authors: G
authors: Zhu
authors: Yan
authors: Y
authors: Li
authors: Changxuan
authors: C
authors: Liu
authors: Ru
authors: R
authors: Yang
authors: Zhiqing
authors: Z
authors: Tang
authors: Jie
authors: J
authors: Li
authors: Wei
authors: W
authors: Huang
authors: Lang
authors: L
authors: Chen
authors: Xiaoling
authors: X
authors: Zheng
authors: Yuling
authors: Y
authors: He
authors: Jinquan
authors: J
authors: Tan
mesh_terms: D001343:Autophagy; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress; D006367:HeLa Cells / Q000166:cytology* / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D012367:RNA, Viral / Q000378:metabolism; D014027:Tobacco Mosaic Virus / Q000502:physiology*
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D012367:RNA, Viral