Autophagy in coxsackievirus-infected neurons.
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.
Yoon
Seung-Yong
SY
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.
Ha
Young-Eun
YE
Choi
Jung-Eun
JE
Ahn
Jeonghyun
J
Lee
Heuiran
H
Kim
Dong-Hou
DH
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
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