title: Mutations in VP2 and VP1 capsid proteins increase infectivity and mouse lethality of enterovirus 71 by virus binding and RNA accumulation enhancement.
abstract: Enterovirus 71 (EV71) is a major cause of hand-foot-and-mouth disease. EV71 infection occasionally associates with severe neurological sequelae such as brainstem encephalitis or poliovirus-like paralysis. We demonstrated that mouse-adapted strain increases infectivity, resulting in higher cytotoxicity of neuron cells and mortality to neonatal mice than a non-adapted strain. Results pointed to EV71 capsid region determining viral infectivity and mouse lethality. Mutant virus with lysine to methionine substitution at VP2(149) (VP2(149M)) or glutamine to glutamic acid substitution at VP1(145) (VP1(145E)) showed greater viral titers and apoptosis. Synergistic effect of VP2(149M) and VP1(145E) double mutations enhanced viral binding and RNA accumulation in infected Neuro-2a cells. The dual substitution mutants markedly reduced value of 50% lethal dose in neonatal mice infection, indicating they raised mouse lethality in vivo. In sum, VP2(149M) and VP1(145E) mutations cooperatively promote viral binding and RNA accumulation of EV71, contributing to viral infectivity in vitro and mouse lethality in vivo.
authors.affiliation: The Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Sheng-Wen
authors.initials: SW
authors.lastname: Huang
authors.forename: Ya-Fang
authors.initials: YF
authors.lastname: Wang
authors.forename: Chun-Keung
authors.initials: CK
authors.lastname: Yu
authors.forename: Ih-Jen
authors.initials: IJ
authors.lastname: Su
authors.forename: Jen-Ren
authors.initials: JR
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D017209:Apoptosis; D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002522:Chlorocebus aethiops; D029821:Enterovirus A, Human / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity*; D004769:Enterovirus Infections / Q000473:pathology / Q000821:virology*; D014644:Genetic Variation; D006232:Hand, Foot and Mouth Disease / Q000235:genetics / Q000821:virology*; D051379:Mice; D050505:Mutant Proteins / Q000378:metabolism; D009154:Mutation; D012367:RNA, Viral / Q000096:biosynthesis; D014709:Vero Cells; D037521:Virulence Factors; D053585:Virus Attachment
chemical_list: D036022:Capsid Proteins; D050505:Mutant Proteins; D012367:RNA, Viral; D037521:Virulence Factors