title: The VP1 structural protein of enterovirus 71 interacts with human ornithine decarboxylase and gene trap ankyrin repeat.
abstract: Enterovirus 71 (EV71) is a major etiological agent of hand, foot and mouth disease (HFMD). Several outbreaks in East Asia were associated with neurological complications and numerous deaths. EV71 possesses four structural proteins VP1-VP4 that are necessary in the formation of the pentameric icosahedral capsid. The viral capsid contributes to virulence, and VP1 is a prime target for EV71 vaccine development. Using yeast two-hybrid analysis, we demonstrated binding affinity between VP1 and three human proteins, i.e. ornithine decarboxylase (ODC1), gene trap ankyrin repeat (GTAR), and KIAA0697 expressed in brain tissue. These interactions were authenticated by co-immunoprecipitation experiments, and by indirect immunofluorescent confocal microscopy of transfected and EV71-infected Vero cells. The significant interaction between VP1 and ODC1 may compromise the latter's activity, and interfere with polyamine biosynthesis, growth and proliferation of EV71-infected cells. The interaction between VP1 and GTAR is noteworthy, since ankyrin proteins are associated with certain neural cell adhesion molecules and with the CRASH neurological syndrome. Given that VP1 is synthesized in large amounts during productive infection, these viral-host protein interactions may provide insights into the role of VP1 in the pathogenesis of EV71 disease and its neurological complications such as acute flaccid paralysis and encephalitis.
authors.affiliation: Human Genome Laboratory, Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge 117597, Singapore.
authors.forename: Wee M
authors.initials: WM
authors.lastname: Yeo
authors.forename: Vincent T K
authors.initials: VT
authors.lastname: Chow
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000378:metabolism; D001853:Bone Marrow / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000821:virology; D036022:Capsid Proteins / Q000378:metabolism*; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004770:Enterovirus / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D015723:Gene Library; D006232:Hand, Foot and Mouth Disease / Q000821:virology*; D006801:Humans; D047468:Immunoprecipitation; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009955:Ornithine Decarboxylase / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D016601:RNA-Binding Proteins; D013460:Sulfur Isotopes / Q000032:analysis; D014709:Vero Cells
chemical_list: C481273:ANKRD17 protein, human; D000914:Antibodies, Viral; D036022:Capsid Proteins; D004268:DNA-Binding Proteins; D016601:RNA-Binding Proteins; D013460:Sulfur Isotopes; D009955:Ornithine Decarboxylase