國家衛生研究院 NHRI:Item 3990099045/9255
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    題名: Mapping enterovirus A71 antigenic determinants from viral evolution
    作者: Huang, SW;Tai, CH;Fonville, JM;Lin, CH;Wang, SM;Liu, CC;Su, IJ;Smith, DJ;Wang, JR
    貢獻者: Division of Infectious Diseases
    摘要: Human enterovirus A71 (EV-A71) belongs to the Enterovirus A species in the picornaviridae family. Several vaccines against EV-A71, a disease causing severe neurological complications or even death, are currently under development and tested in clinical trials, and preventative vaccination programs are expected to start soon. To characterize the potential for antigenic change of EV-A71, we compared the sequences of two antigenically diverse genotype B4 and B5 strains of EV-A71 and identified substitutions at residues 98, 145, and 164 in the VP1 capsid protein as antigenic determinants. To examine the effect of these three substitutions on antigenicity, we constructed a series of recombinant viruses containing different mutation combinations at these three residues with a reverse genetics system and then investigated the molecular basis of antigenic changes with antigenic cartography. We found that a novel EV-A71 mutant, containing lysine, glutamine, and glutamic acid at the respective residues 98, 145, and 164 in the VP1 capsid protein, exhibited neutralization reduction against patients' antisera and substantially increased virus binding ability to human cells. These observations indicated that this low neutralization-reactive EV-A71 VP1-98K/145Q/164E mutant potentially increases viral binding ability, and that surveillance studies should look out for these mutants that could compromise vaccine efficacy. IMPORTANCE: Emerging and re-emerging EV-A71 viruses can cause severe neurological etiology, primarily affecting children, especially around Asia-Pacific countries. We identified a set of mutations in EV-A71 that both reduced neutralization activity against humoral immunity in antisera of patients and healthy adults and greatly increased the viral binding ability to cells. These findings provide important insights for EV-A71 antigenic determinants, and emphasize the importance of continuous surveillance, especially after EV-A71 vaccination programs begin.
    日期: 2015-11
    關聯: Journal of Virology. 2015 Nov;89(22):11500-11506.
    Link to: http://dx.doi.org/10.1128/jvi.02035-15
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0022-538X&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000363467200027
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84945952706
    顯示於類別:[蘇益仁(2002-2015)] 期刊論文

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