title: The association of receptor of activated protein kinase C 1(RACK1) with infectious bursal disease virus viral protein VP5 and voltage-dependent anion channel 2 (VDAC2) inhibits apoptosis and enhances viral replication.
abstract: Infectious bursal disease (IBD) is an acute, highly contagious, and immunosuppressive avian disease caused by IBD virus (IBDV). Our previous report indicates that IBDV VP5 induces apoptosis via interaction with voltage-dependent anion channel 2 (VDAC2). However, the underlying molecular mechanism is still unclear. We report here that receptor of activated protein kinase C 1 (RACK1) interacts with both VDAC2 and VP5 and that they could form a complex. We found that overexpression of RACK1 inhibited IBDV-induced apoptosis in DF-1 cells and that knockdown of RACK1 by small interfering RNA induced apoptosis associated with activation of caspases 9 and 3 and suppressed IBDV growth. These results indicate that RACK1 plays an antiapoptotic role during IBDV infection via interaction with VDAC2 and VP5, suggesting that VP5 sequesters RACK1 and VDAC2 in the apoptosis-inducing process.
authors.affiliation: From the State Key Laboratory of Agrobiotechnology, Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, and College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
authors.forename: Wencheng
authors.initials: W
authors.lastname: Lin
authors.affiliation: From the State Key Laboratory of Agrobiotechnology, Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, and College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: From the State Key Laboratory of Agrobiotechnology, Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, and College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Xu
authors.affiliation: From the State Key Laboratory of Agrobiotechnology, Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, and College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: From the State Key Laboratory of Agrobiotechnology, Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, and College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
authors.forename: Xiaoqi
authors.initials: X
authors.lastname: Li
authors.affiliation: From the State Key Laboratory of Agrobiotechnology, Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, and College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Cao
authors.affiliation: From the State Key Laboratory of Agrobiotechnology, Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, and College of Veterinary Medicine, China Agricultural University, Beijing 100193, China vetwyq@cau.edu.cn.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: From the State Key Laboratory of Agrobiotechnology, Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, and College of Veterinary Medicine, China Agricultural University, Beijing 100193, China sjzheng@cau.edu.cn.
authors.forename: Shijun J
authors.initials: SJ
authors.lastname: Zheng
mesh_terms: D000818:Animals; D002645:Chickens; D019204:GTP-Binding Proteins / Q000502:physiology*; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D007243:Infectious bursal disease virus / Q000502:physiology*; D009363:Neoplasm Proteins / Q000502:physiology*; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000502:physiology*; D017361:Viral Nonstructural Proteins / Q000502:physiology*; D014779:Virus Replication; D050996:Voltage-Dependent Anion Channel 2 / Q000378:metabolism*
chemical_list: D009363:Neoplasm Proteins; C419368:RACK1 protein, human; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; C494765:VDAC2 protein, human; C518635:VP5 protein, infectious bursal disease virus; D017361:Viral Nonstructural Proteins; D050996:Voltage-Dependent Anion Channel 2; D019204:GTP-Binding Proteins
keywords: Apoptosis; Caspase; Host-Pathogen Interaction; Infectious Bursal Disease Virus (IBDV); Protein Complex; Receptor of Activated Protein Kinase C 1 (RACK1); Viral Replication; Voltage-dependent Anion Channel (VDAC); Yeast Two-hybrid