title: Coxsackievirus B3-induced calpain activation facilitates the progeny virus replication via a likely mechanism related with both autophagy enhancement and apoptosis inhibition in the early phase of infection: an in vitro study in H9c2 cells.
abstract: Calpain is a family of neutral cysteine proteinase involved in many physiological and pathological processes including virus replication, autophagy and apoptosis. Previous study has indicated the involvement of calpain in pathogenesis of coxsackievirus B3 (CVB3)-induced myocarditis. Besides, many studies demonstrated that host cell autophagy and apoptosis mechanisms participate in virus life cycle. However, role of calpain in CVB3 replication via autophagy/apoptosis mechanisms has not been reported, which was discussed here in H9c2 cardiomyocytes. The data demonstrated that calpain was activated following CVB3 infection. Calpain inhibition decreased autophagy, indicating role of calpain in enhancing autophagy during CVB3 infection. Both calpain activity and autophagy were involved in facilitating CVB3 replication demonstrated by virus titer and CVB3 capsid protein VP1 expression alterations resulting from calpain inhibitor ALLN and autophagy inhibitor 3MA intervention. We also found that both calpain activity and autophagy suppressed caspase3 activity and host cell apoptosis 5-10h post-infection (p.i.). In summary, the present study shows that CVB3 infection of H9c2 cells hinders caspase3 activity provocation and cell apoptosis at least in the early phase of infection (5-10h p.i.) via calpain-induced autophagy enhancement, which might be a mechanism facilitating CVB3 replication in host cells.
authors.affiliation: Key Laboratory of Viral Heart Diseases, Ministry of Public Health, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, China.
authors.forename: Minghui
authors.initials: M
authors.lastname: Li
authors.affiliation: Key Laboratory of Viral Heart Diseases, Ministry of Public Health, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, China.
authors.forename: Xinggang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Viral Heart Diseases, Ministry of Public Health, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Key Laboratory of Viral Heart Diseases, Ministry of Public Health, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Key Laboratory of Viral Heart Diseases, Ministry of Public Health, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, China.
authors.forename: Yeqing
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Key Laboratory of Viral Heart Diseases, Ministry of Public Health, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, China.
authors.forename: Yunzeng
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Key Laboratory of Viral Heart Diseases, Ministry of Public Health, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, China.
authors.forename: Junbo
authors.initials: J
authors.lastname: Ge
authors.affiliation: Lawson Health Research Institute, Department of Medicine and Pathology, University of Western Ontario, Canada.
authors.forename: Tianqing
authors.initials: T
authors.lastname: Peng
authors.affiliation: Key Laboratory of Viral Heart Diseases, Ministry of Public Health, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, China. Electronic address: chen.ruizhen@zs-hospital.sh.cn.
authors.forename: Ruizhen
authors.initials: R
authors.lastname: Chen
mesh_terms: D017209:Apoptosis; D001343:Autophagy; D002154:Calpain / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003384:Coxsackievirus Infections / Q000201:enzymology* / Q000503:physiopathology / Q000821:virology*; D029822:Enterovirus B, Human / Q000235:genetics / Q000502:physiology*; D004789:Enzyme Activation; D006801:Humans; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
chemical_list: D014764:Viral Proteins; D002154:Calpain
keywords: Apoptosis; Autophagy; Calpain; Coxsackievirus B3; H9c2 cells