title: Coxsackievirus A16 elicits incomplete autophagy involving the mTOR and ERK pathways.
abstract: Autophagy is an important homeostatic process for the degradation of cytosolic proteins and organelles and has been reported to play an important role in cellular responses to pathogens and virus replication. However, the role of autophagy in Coxsackievirus A16 (CA16) infection and pathogenesis remains unknown. Here, we demonstrated that CA16 infection enhanced autophagosome formation, resulting in increased extracellular virus production. Moreover, expression of CA16 nonstructural proteins 2C and 3C was sufficient to trigger autophagosome accumulation by blocking the fusion of autophagosomes with lysosomes. Interestingly, we found that Immunity-related GTPase family M (IRGM) was crucial for the activation of CA16 infection-induced autophagy; in turn, reducing IRGM expression suppressed autophagy. Expression of viral protein 2C enhanced IRGM promoter activation, thereby increasing IRGM expression and inducing autophagy. CA16 infection inhibited Akt/mTOR signaling and activated extracellular signal-regulated kinase (ERK) signaling, both of which are necessary for autophagy induction. In summary, CA16 can use autophagy to enhance its own replication. These results raise the possibility of targeting the autophagic pathway for the treatment of hand, foot, and mouth disease (HFMD).
authors: Pathogenic Organism and Infectious Diseases Research Institute, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, China; Hubei Province Key Laboratory of Allergy and Immunology, Wuhan, 430071, China.
authors: Yingying
authors: Y
authors: Shi
authors: Pathogenic Organism and Infectious Diseases Research Institute, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, China; Hubei Provincial Key Laboratory of Developmentally Originated Disease, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
authors: Xiaohua
authors: X
authors: He
authors: Pathogenic Organism and Infectious Diseases Research Institute, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, China; Intensive Care Unit of Emergency Department, Wuhan General Hospital of Guangzhou Command, Wuhan, 430071, China.
authors: Guoguo
authors: G
authors: Zhu
authors: Pathogenic Organism and Infectious Diseases Research Institute, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, China.
authors: Huilin
authors: H
authors: Tu
authors: Institute of Neuropsychiatry, Renmin Hospital, Wuhan University, Wuhan, 430060, China.
authors: Zhongchun
authors: Z
authors: Liu
authors: College of Life Sciences, Wuhan University, Wuhan, 430072, P R China.
authors: Wenhua
authors: W
authors: Li
authors: Pathogenic Organism and Infectious Diseases Research Institute, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, China.
authors: Song
authors: S
authors: Han
authors: Pathogenic Organism and Infectious Diseases Research Institute, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, China.
authors: Jun
authors: J
authors: Yin
authors: Pathogenic Organism and Infectious Diseases Research Institute, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, China; Hubei Provincial Key Laboratory of Developmentally Originated Disease, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
authors: Biwen
authors: B
authors: Peng
authors: Pathogenic Organism and Infectious Diseases Research Institute, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, China; Hubei Province Key Laboratory of Allergy and Immunology, Wuhan, 430071, China.
authors: Wanhong
authors: W
authors: Liu
mesh_terms: D001343:Autophagy / Q000235:genetics*; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics*; D003384:Coxsackievirus Infections / Q000235:genetics* / Q000821:virology; D004770:Enterovirus / Q000235:genetics* / Q000472:pathogenicity; D019204:GTP-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D015967:Gene Expression Regulation, Viral; D006367:HeLa Cells; D006801:Humans; D008247:Lysosomes / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000235:genetics; D017361:Viral Nonstructural Proteins / Q000096:biosynthesis / Q000235:genetics*; D014779:Virus Replication / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D017361:Viral Nonstructural Proteins; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; C076023:2C protein, viral; D019204:GTP-Binding Proteins; C513539:IRGM protein, human