title: Rabies virus matrix protein induces apoptosis by targeting mitochondria.
abstract: Apoptosis, as an innate antiviral defense, not only functions to limit viral replication by eliminating infected cells, but also contribute to viral dissemination, particularly at the late stages of infection. A highly neurotropic CVS strain of rabies virus induces apoptosis both in vitro and in vivo. However, the detailed mechanism of CVS-mediated neuronal apoptosis is not entirely clear. Here, we show that CVS induces apoptosis through mitochondrial pathway by dissipating mitochondrial membrane potential, release of cytochrome c and AIF. CVS blocks Bax activation at the early stages of infection; while M protein partially targets mitochondria and induces mitochondrial apoptosis at the late stages of infection. The α-helix structure spanning 67-79 amino acids of M protein is essential for mitochondrial targeting and induction of apoptosis. These results suggest that CVS functions on mitochondria to regulate apoptosis at different stages of infection, so as to for viral replication and dissemination.
authors.affiliation: Key Laboratory of Animal Virology of Ministry of Agriculture, Zhejiang University, Hangzhou, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zan
authors.affiliation: Key Laboratory of Animal Virology of Ministry of Agriculture, Zhejiang University, Hangzhou, PR China.
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.affiliation: Key Laboratory of Animal Virology of Ministry of Agriculture, Zhejiang University, Hangzhou, PR China.
authors.forename: Jian-Wei
authors.initials: JW
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Animal Virology of Ministry of Agriculture, Zhejiang University, Hangzhou, PR China.
authors.forename: Hai-Long
authors.initials: HL
authors.lastname: Wang
authors.affiliation: Key Laboratory of Animal Virology of Ministry of Agriculture, Zhejiang University, Hangzhou, PR China.
authors.forename: Kai-Kun
authors.initials: KK
authors.lastname: Mo
authors.affiliation: Key Laboratory of Animal Virology of Ministry of Agriculture, Zhejiang University, Hangzhou, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Key Laboratory of Animal Virology of Ministry of Agriculture, Zhejiang University, Hangzhou, PR China.
authors.forename: Yun-Bin
authors.initials: YB
authors.lastname: Xu
authors.affiliation: Key Laboratory of Animal Virology of Ministry of Agriculture, Zhejiang University, Hangzhou, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Liao
authors.affiliation: Institute of Immunology, Nanjing Agricultural University, Nanjing, PR China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Su
authors.affiliation: Laboratory of Epidemiology, Veterinary Institute, Academy of military Medical Sciences, Changchun, PR China.
authors.forename: Rong-Liang
authors.initials: RL
authors.lastname: Hu
authors.affiliation: Key Laboratory of Animal Virology of Ministry of Agriculture, Zhejiang University, Hangzhou, PR China; Collaborative Innovation Center and State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University, Hangzhou, PR China; Institute of Immunology, Nanjing Agricultural University, Nanjing, PR China. Electronic address: jyzhou@zju.edu.cn.
authors.forename: Ji-Yong
authors.initials: JY
authors.lastname: Zhou
mesh_terms: D000818:Animals; D017209:Apoptosis; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002460:Cell Line; D004789:Enzyme Activation; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D011818:Rabies / Q000378:metabolism / Q000821:virology; D011820:Rabies virus / Q000378:metabolism*; D015398:Signal Transduction; D014763:Viral Matrix Proteins / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D051033:Apoptosis Inducing Factor; D014763:Viral Matrix Proteins; D051028:bcl-2-Associated X Protein; D053453:Caspase 9
keywords: Apoptosis; Matrix protein; Mitochondria; Rabies virus