title: Autophagy Negatively Regulates Transmissible Gastroenteritis Virus Replication.
abstract: Autophagy is an evolutionarily ancient pathway that has been shown to be important in the innate immune defense against several viruses. However, little is known about the regulatory role of autophagy in transmissible gastroenteritis virus (TGEV) replication. In this study, we found that TGEV infection increased the number of autophagosome-like double- and single-membrane vesicles in the cytoplasm of host cells, a phenomenon that is known to be related to autophagy. In addition, virus replication was required for the increased amount of the autophagosome marker protein LC3-II. Autophagic flux occurred in TGEV-infected cells, suggesting that TGEV infection triggered a complete autophagic response. When autophagy was pharmacologically inhibited by wortmannin or LY294002, TGEV replication increased. The increase in virus yield via autophagy inhibition was further confirmed by the use of siRNA duplexes, through which three proteins required for autophagy were depleted. Furthermore, TGEV replication was inhibited when autophagy was activated by rapamycin. The antiviral response of autophagy was confirmed by using siRNA to reduce the expression of gene p300, which otherwise inhibits autophagy. Together, the results indicate that TGEV infection activates autophagy and that autophagy then inhibits further TGEV replication.
authors.affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
authors.forename: Longjun
authors.initials: L
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.|Weike Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
authors.forename: Haidong
authors.initials: H
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
authors.forename: Weihong
authors.initials: W
authors.lastname: Gu
authors.affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
authors.forename: Ren
authors.initials: R
authors.lastname: Li
authors.affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
authors.forename: Li
authors.initials: L
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects / Q000235:genetics*; D000071187:Autophagy-Related Protein 5 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000071193:Autophagy-Related Protein 7 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D022162:Cytoplasmic Vesicles / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D010588:Phagosomes / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D013552:Swine; D005760:Transmissible gastroenteritis virus / Q000472:pathogenicity / Q000502:physiology*; D014779:Virus Replication / Q000187:drug effects; D000077191:Wortmannin; D050880:p300-CBP Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D000099224:p300-CBP-Associated Factor
chemical_list: D000730:Androstadienes; D000911:Antibodies, Monoclonal; D000071187:Autophagy-Related Protein 5; D000071193:Autophagy-Related Protein 7; D002867:Chromones; D008869:Microtubule-Associated Proteins; D009025:Morpholines; D034741:RNA, Small Interfering; D020123:Sirolimus; D000077191:Wortmannin; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one