title: BECN1-dependent CASP2 incomplete autophagy induction by binding to rabies virus phosphoprotein.
abstract: Autophagy is an essential component of host immunity and used by viruses for survival. However, the autophagy signaling pathways involved in virus replication are poorly documented. Here, we observed that rabies virus (RABV) infection triggered intracellular autophagosome accumulation and results in incomplete autophagy by inhibiting autophagy flux. Subsequently, we found that RABV infection induced the reduction of CASP2/caspase 2 and the activation of AMP-activated protein kinase (AMPK)-AKT-MTOR (mechanistic target of rapamycin) and AMPK-MAPK (mitogen-activated protein kinase) pathways. Further investigation revealed that BECN1/Beclin 1 binding to viral phosphoprotein (P) induced an incomplete autophagy via activating the pathways CASP2-AMPK-AKT-MTOR and CASP2-AMPK-MAPK by decreasing CASP2. Taken together, our data first reveals a crosstalk of BECN1 and CASP2-dependent autophagy pathways by RABV infection.
authors.affiliation: a Key Laboratory of Animal Virology of Ministry of Agriculture , Zhejiang University , Hangzhou , China.
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.affiliation: a Key Laboratory of Animal Virology of Ministry of Agriculture , Zhejiang University , Hangzhou , China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Wang
authors.affiliation: b Institute of Immunology and College of Veterinary Medicine, Nanjing Agricultural University , Nanjing , China.
authors.forename: Jinyan
authors.initials: J
authors.lastname: Gu
authors.affiliation: a Key Laboratory of Animal Virology of Ministry of Agriculture , Zhejiang University , Hangzhou , China.
authors.forename: Tingjuan
authors.initials: T
authors.lastname: Deng
authors.affiliation: a Key Laboratory of Animal Virology of Ministry of Agriculture , Zhejiang University , Hangzhou , China.
authors.forename: Zhuangchuan
authors.initials: Z
authors.lastname: Yuan
authors.affiliation: b Institute of Immunology and College of Veterinary Medicine, Nanjing Agricultural University , Nanjing , China.
authors.forename: Boli
authors.initials: B
authors.lastname: Hu
authors.affiliation: a Key Laboratory of Animal Virology of Ministry of Agriculture , Zhejiang University , Hangzhou , China.
authors.forename: Yunbin
authors.initials: Y
authors.lastname: Xu
authors.affiliation: a Key Laboratory of Animal Virology of Ministry of Agriculture , Zhejiang University , Hangzhou , China.|c Collaborative Innovation Center and State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, Zhejiang University , Hangzhou , China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yan
authors.affiliation: a Key Laboratory of Animal Virology of Ministry of Agriculture , Zhejiang University , Hangzhou , China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zan
authors.affiliation: a Key Laboratory of Animal Virology of Ministry of Agriculture , Zhejiang University , Hangzhou , China.|c Collaborative Innovation Center and State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, Zhejiang University , Hangzhou , China.
authors.forename: Min
authors.initials: M
authors.lastname: Liao
authors.affiliation: d Department of Veterinary Biosciences , College of Veterinary Medicine, Ohio State University , Columbus , OH , USA.
authors.forename: Erin
authors.initials: E
authors.lastname: DiCaprio
authors.affiliation: d Department of Veterinary Biosciences , College of Veterinary Medicine, Ohio State University , Columbus , OH , USA.
authors.forename: Jianrong
authors.initials: J
authors.lastname: Li
authors.affiliation: b Institute of Immunology and College of Veterinary Medicine, Nanjing Agricultural University , Nanjing , China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Su
authors.affiliation: a Key Laboratory of Animal Virology of Ministry of Agriculture , Zhejiang University , Hangzhou , China.|c Collaborative Innovation Center and State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, Zhejiang University , Hangzhou , China.
authors.forename: Jiyong
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000071182:Autophagosomes / Q000378:metabolism; D001343:Autophagy; D000071186:Beclin-1 / Q000378:metabolism*; D053143:Caspase 2 / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D018832:Molecular Chaperones; D010750:Phosphoproteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011818:Rabies / Q000378:metabolism / Q000473:pathology / Q000821:virology; D011820:Rabies virus / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D015678:Viral Structural Proteins / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D000071186:Beclin-1; D018832:Molecular Chaperones; C103961:P phosphoprotein, Rabies virus; D010750:Phosphoproteins; D015678:Viral Structural Proteins; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C090208:Casp2 protein, mouse; D053143:Caspase 2
keywords: BECN1; CASP2-dependent pathway; RABV; autophagy; viral protein P