title: Autophagy in coxsackievirus-infected neurons.
abstract: Autophagy is a process to engulf aberrant organelles or protein aggregates into double-membrane vesicles for lysosomal breakdown. Autophagy is a protective process against some intracellular bacteria and viruses; however, it is also used for replication by some viruses, such as poliovirus. We recently found that coxsackievirus B4 (CVB4) also induces the autophagy pathway and activates the calpain system for replication in neurons. Notably, the inhibition of autophagy with 3-methyladenine (3MA) reduced calpain activation and virus replication. Calpain inhibitors also reduced autophagosome formation and virus replication. This finding indicates that calpain and the autophagy pathway are closely connected with each other during the infection. Interestingly, we also found that 3MA and calpain inhibitors enhanced the caspase-3 specific cleavage of spectrin during CVB4 infection, suggesting that autophagy inhibition by these drugs triggered apoptosis. Thus, autophagy and apoptosis may balance each other in CVB4-infected neurons. Here, we show that inhibition of caspase with zVAD increased autophagosome formation, further proposing the cross-talk between autophagy and apoptosis in CVB4-infected neurons.
authors.affiliation: Department of Anatomy & Cell Biology and Research Institute for Biomacromolecules, University of Ulsan College of Medicine and Department of Forensic Medicine, National Institute of Scientific Investigation, Seoul, Korea.
authors.forename: Seung-Yong
authors.initials: SY
authors.lastname: Yoon
authors.forename: Young-Eun
authors.initials: YE
authors.lastname: Ha
authors.forename: Jung-Eun
authors.initials: JE
authors.lastname: Choi
authors.forename: Jeonghyun
authors.initials: J
authors.lastname: Ahn
authors.forename: Heuiran
authors.initials: H
authors.lastname: Lee
authors.forename: Dong-Hou
authors.initials: DH
authors.lastname: Kim
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000378:metabolism; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D001343:Autophagy / Q000502:physiology*; D002154:Calpain / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D003384:Coxsackievirus Infections / Q000378:metabolism* / Q000821:virology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism / Q000821:virology; D051381:Rats; D020123:Sirolimus / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D015853:Cysteine Proteinase Inhibitors; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C025946:3-methyladenine; D002154:Calpain; D020169:Caspases; D000225:Adenine; D020123:Sirolimus