title: The C-terminal amyloidogenic peptide contributes to self-assembly of Avibirnavirus viral protease.
abstract: Unlike other viral protease, Avibirnavirus infectious bursal disease virus (IBDV)-encoded viral protease VP4 forms unusual intracellular tubule-like structures during viral infection. However, the formation mechanism and potential biological functions of intracellular VP4 tubules remain largely elusive. Here, we show that VP4 can assemble into tubules in diverse IBDV-infected cells. Dynamic analysis show that VP4 initiates the assembly at early stage of IBDV infection, and gradually assembles into larger size of fibrils within the cytoplasm and nucleus. Intracellular assembly of VP4 doesn't involve the host cytoskeleton, other IBDV-encoded viral proteins or vital subcellular organelles. Interestingly, the last C-terminal hydrophobic and amyloidogenic stretch (238)YHLAMA(243) with two "aggregation-prone" alanine residues was found to be essential for its intracellular self-assembly. The assembled VP4 fibrils show significantly low solubility, subsequently, the deposition of highly assembled VP4 structures ultimately deformed the host cytoskeleton and nucleus, which was potentially associated with IBDV lytic infection. Importantly, the assembly of VP4 significantly reduced the cytotoxicity of protease activity in host cells which potentially prevent the premature cell death and facilitate viral replication. This study provides novel insights into the formation mechanism and biological functions of the Avibirnavirus protease-related fibrils.
authors.affiliation: Key Laboratory of Animal Virology of Ministry of Agriculture, Zhejiang University, Hangzhou 310058, PR China.|State Key Laboratory and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, Zhejiang University, Hangzhou 310003, PR China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Animal Virology of Ministry of Agriculture, Zhejiang University, Hangzhou 310058, PR China.
authors.forename: Lu
authors.initials: L
authors.lastname: Jia
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR China.
authors.forename: Boli
authors.initials: B
authors.lastname: Hu
authors.affiliation: Key Laboratory of Animal Virology of Ministry of Agriculture, Zhejiang University, Hangzhou 310058, PR China.
authors.forename: Yanting
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Key Laboratory of Animal Virology of Ministry of Agriculture, Zhejiang University, Hangzhou 310058, PR China.
authors.forename: Yina
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Animal Virology of Ministry of Agriculture, Zhejiang University, Hangzhou 310058, PR China.
authors.forename: Xiangxiang
authors.initials: X
authors.lastname: Gao
authors.affiliation: Key Laboratory of Animal Virology of Ministry of Agriculture, Zhejiang University, Hangzhou 310058, PR China.
authors.forename: Tingjuan
authors.initials: T
authors.lastname: Deng
authors.affiliation: Key Laboratory of Animal Virology of Ministry of Agriculture, Zhejiang University, Hangzhou 310058, PR China.
authors.forename: Shengjun
authors.initials: S
authors.lastname: Bao
authors.affiliation: Key Laboratory of Animal Virology of Ministry of Agriculture, Zhejiang University, Hangzhou 310058, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.affiliation: Key Laboratory of Animal Virology of Ministry of Agriculture, Zhejiang University, Hangzhou 310058, PR China.|State Key Laboratory and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, Zhejiang University, Hangzhou 310003, PR China.|College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR China.
authors.forename: Jiyong
authors.initials: J
authors.lastname: Zhou
mesh_terms: D058227:Amyloidogenic Proteins / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D019202:Avibirnavirus / Q000378:metabolism* / Q000472:pathogenicity; D002642:Chick Embryo; D002522:Chlorocebus aethiops; D003599:Cytoskeleton / Q000378:metabolism; D057809:HEK293 Cells / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D007243:Infectious bursal disease virus / Q000378:metabolism / Q000472:pathogenicity; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D012697:Serine Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D012995:Solubility; D014709:Vero Cells / Q000821:virology; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism*; D015678:Viral Structural Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D058227:Amyloidogenic Proteins; D010455:Peptides; C478245:VP4 protein, infectious bursal disease virus; D014764:Viral Proteins; D015678:Viral Structural Proteins; D012697:Serine Endopeptidases