title: Identification of a common epitope between enterovirus 71 and human MED25 proteins which may explain virus-associated neurological disease.
abstract: Enterovirus 71 (EV71) is a major causative pathogen of hand, foot and mouth disease with especially severe neurologic complications, which mainly account for fatalities from this disease. To date, the pathogenesis of EV71 in the central neurons system has remained unclear. Cytokine-mediated immunopathogenesis and nervous tissue damage by virus proliferation are two widely speculated causes of the neurological disease. To further study the pathogenesis, we identified a common epitope (co-epitope) between EV71 VP1 and human mediator complex subunit 25 (MED25) highly expressed in brain stem. A monoclonal antibody (2H2) against the co-epitope was prepared, and its interaction with MED25 was examined by ELISA, immunofluorescence assay and Western blot in vitro and by live small animal imaging in vivo. Additionally, 2H2 could bind to both VP1 and MED25 with the affinity constant (Kd) of 10-7 M as determined by the ForteBio Octet System. Intravenously injected 2H2 was distributed in brain stem of mice after seven days of EV71 infection. Interestingly, 2H2-like antibodies were detected in the serum of EV71-infected patients. These findings suggest that EV71 infection induces the production of antibodies that can bind to autoantigens expressed in nervous tissue and maybe further trigger autoimmune reactions resulting in neurological disease.
authors.affiliation: School of Life Sciences, Jilin University, Changchun 130012, China. fph121@163.com.|National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun 130012, China. fph121@163.com.
authors.forename: Peihu
authors.initials: P
authors.lastname: Fan
authors.affiliation: School of Life Sciences, Jilin University, Changchun 130012, China. lixiaojun3345@163.com.|National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun 130012, China. lixiaojun3345@163.com.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Li
authors.affiliation: School of Life Sciences, Jilin University, Changchun 130012, China. sunsy121@163.com.|National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun 130012, China. sunsy121@163.com.
authors.forename: Shiyang
authors.initials: S
authors.lastname: Sun
authors.affiliation: School of Life Sciences, Jilin University, Changchun 130012, China. suweiheng@163.com.|National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun 130012, China. suweiheng@163.com.
authors.forename: Weiheng
authors.initials: W
authors.lastname: Su
authors.affiliation: School of Life Sciences, Jilin University, Changchun 130012, China. andonginlab@sina.cn.|National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun 130012, China. andonginlab@sina.cn.
authors.forename: Dong
authors.initials: D
authors.lastname: An
authors.affiliation: School of Life Sciences, Jilin University, Changchun 130012, China. feng0215@gmail.com.|National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun 130012, China. feng0215@gmail.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.affiliation: School of Life Sciences, Jilin University, Changchun 130012, China.|National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun 130012, China.|Key Laboratory for Molecular Enzymology and Engineering, Jilin University, Changchun 130012, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Kong
authors.affiliation: School of Life Sciences, Jilin University, Changchun 130012, China. jiangcl@jlu.edu.cn.|National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun 130012, China. jiangcl@jlu.edu.cn.|Key Laboratory for Molecular Enzymology and Engineering, Jilin University, Changchun 130012, China. jiangcl@jlu.edu.cn.
authors.forename: Chunlai
authors.initials: C
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000302:isolation & purification; D000914:Antibodies, Viral / Q000276:immunology / Q000302:isolation & purification; D001324:Autoantigens / Q000276:immunology; D015153:Blotting, Western; D001933:Brain Stem / Q000473:pathology; D029821:Enterovirus A, Human / Q000276:immunology*; D004769:Enterovirus Infections / Q000150:complications* / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D056892:Mediator Complex / Q000276:immunology*; D051379:Mice; D009422:Nervous System Diseases / Q000209:etiology*; D015678:Viral Structural Proteins / Q000276:immunology*; D051598:Whole Body Imaging
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D001324:Autoantigens; D000939:Epitopes; C483045:MED25 protein, human; D056892:Mediator Complex; D015678:Viral Structural Proteins
references.citation: Lancet. 1999 Nov 13;354(9191):1682-6
references.pmid: 10568570
references.citation: Annu Rev Biochem. 2000;69:729-49
references.pmid: 10966474
references.citation: J Virol. 2001 Aug;75(16):7732-8
references.pmid: 11462047
references.citation: Vaccine. 2001 Dec 12;20(5-6):895-904
references.pmid: 11738755
references.citation: FEMS Microbiol Rev. 2002 Mar;26(1):91-107
references.pmid: 12007645
references.citation: Acta Paediatr. 2002;91(6):632-5
references.pmid: 12162592
references.citation: Clin Infect Dis. 2003 Feb 1;36(3):269-74
references.pmid: 12539066
references.citation: J Med Virol. 2003 May;70(1):109-18
references.pmid: 12629651
references.citation: Emerg Infect Dis. 2003 Apr;9(4):461-8
references.pmid: 12702227
references.citation: J Infect Dis. 2003 Aug 15;188(4):564-70
references.pmid: 12898444
references.citation: EMBO J. 2003 Dec 15;22(24):6494-504
references.pmid: 14657022
references.citation: J Infect Dis. 1974 Mar;129(3):304-9
references.pmid: 4361245
references.citation: J Infect Dis. 1986 Mar;153(3):498-502
references.pmid: 3005425
references.citation: Curr Top Microbiol Immunol. 1990;161:121-54
references.pmid: 2169382
references.citation: Int J Cancer. 1991 Jan 21;47(2):267-73
references.pmid: 1703128
references.citation: Cell. 1991 Apr 19;65(2):319-31
references.pmid: 1901765
references.citation: Neurotoxicology. 1992 Spring;13(1):171-7
references.pmid: 1324447
references.citation: Virus Res. 1995 Sep;38(1):1-24
references.pmid: 8546007
references.citation: Immunol Rev. 1996 Aug;152:21-45
references.pmid: 8930666
references.citation: Chest. 1997 Dec;112(6 Suppl):321S-329S
references.pmid: 9400897
references.citation: Cold Spring Harb Symp Quant Biol. 1998;63:167-71
references.pmid: 10384280
references.citation: Immunol Rev. 1999 Jun;169:241-53
references.pmid: 10450521
references.citation: Pediatr Infect Dis J. 1999 Dec;18(12):1092-6
references.pmid: 10608631
references.citation: Cytokine. 2005 Feb 21;29(4):169-75
references.pmid: 15652449
references.citation: J Clin Virol. 2006 Sep;37(1):47-52
references.pmid: 16861032
references.citation: Curr Med Chem. 2007;14(8):847-56
references.pmid: 17430140
references.citation: Clin Infect Dis. 2007 Oct 15;45(8):950-7
references.pmid: 17879907
references.citation: J Neuropathol Exp Neurol. 2008 Jun;67(6):532-42
references.pmid: 18520772
references.citation: Adv Virus Res. 2008;71:1-50
references.pmid: 18585526
references.citation: J Clin Neurosci. 2008 Sep;15(9):961-71
references.pmid: 18411052
references.citation: Lancet Neurol. 2008 Dec;7(12):1091-8
references.pmid: 18851928
references.citation: J Clin Microbiol. 2009 Jul;47(7):2351-2
references.pmid: 19439545
references.citation: Ann Neurol. 2009 Jul;66(1):11-8
references.pmid: 19670433
references.citation: Virol J. 2010;7:47
references.pmid: 20170551
references.citation: Lancet Neurol. 2010 Nov;9(11):1097-105
references.pmid: 20965438
references.citation: Lancet Infect Dis. 2010 Nov;10(11):778-90
references.pmid: 20961813
references.citation: J Virol. 2011 Apr;85(7):3067-76
references.pmid: 21228224
references.citation: Proc Natl Acad Sci U S A. 2011 Jul 12;108(28):11560-5
references.pmid: 21700885
references.citation: Epidemiology. 2011 Nov;22(6):781-92
references.pmid: 21968769
references.citation: Biochimie. 2012 Mar;94(3):579-87
references.pmid: 21983542
references.citation: PLoS Pathog. 2012;8(7):e1002826
references.pmid: 22910880
references.citation: PLoS Negl Trop Dis. 2012;6(8):e1737
references.pmid: 22953003
references.citation: Clin Dev Immunol. 2012;2012:876241
references.pmid: 22956971
references.citation: J Exp Med. 2013 Feb 11;210(2):241-56
references.pmid: 23359068
references.citation: Virol J. 2013;10:250
references.pmid: 23919614
references.citation: Virus Genes. 2014 Apr;48(2):260-72
references.pmid: 24442718
references.citation: PLoS One. 2014;9(6):e100545
references.pmid: 24964084
references.citation: Biochim Biophys Acta. 1971 Dec 28;251(3):427-34
references.pmid: 11452886