title: Enterovirus 71 induces apoptosis by directly modulating the conformational activation of pro-apoptotic protein Bax.
abstract: Enterovirus 71 (EVA71), a virus of the genus Enterovirus in the family Picornaviridae, is one of the main causative agents of hand, foot and mouth disease in infected infants and young children. In this study, we report that cells with EVA71 infection exhibit increased levels of cytochrome c release and caspase-3 activation. EVA71 infection induces the conformational activation of pro-apoptotic protein Bax and the subsequent formation of oligomers of Bax in mitochondria. Inhibitors that block caspase-8 activation cannot inhibit apoptosis induced by EVA71 infection. Importantly, cells with Bax but not Bak or caspase-8 knockdown show resistance to apoptosis induced by EVA71 infection. Mitochondria isolated from EVA71-infected cells display clear Bax-binding ability and the subsequent release of cytochrome c. Therefore, these results indicate that EVA71 infection directly impacts the mitochondrial apoptotic pathway by modulating the recruitment and activation of Bax.
authors.affiliation: College of Life Sciences, Inner Mongolia Agriculture University, No. 306 Zhaowuda Road, Hohhot 010018, Inner Mongolia, PR China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Han
authors.affiliation: Center for Molecular Virology, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, PR China.
authors.forename: Haolong
authors.initials: H
authors.lastname: Cong
mesh_terms: D017209:Apoptosis; D045304:Cytochromes c / Q000378:metabolism; D029821:Enterovirus A, Human / Q000502:physiology*; D006232:Hand, Foot and Mouth Disease / Q000378:metabolism* / Q000821:virology*; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D011487:Protein Conformation; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c