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Structural basis of potent Zika-dengue virus antibody cross-neutralization

机译:寨卡病毒登革热病毒抗体有效中和的结构基础

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摘要

Zika virus is a member of the Flavivirus genus that had not been associated with severe disease in humans until the recent outbreaks, when it was linked to microcephaly in newborns in Brazil and to Guillain-Barre syndrome in adults in French Polynesia. Zika virus is related to dengue virus, and here we report that a subset of antibodies targeting a conformational epitope isolated from patients with dengue virus also potently neutralize Zika virus. The crystal structure of two of these antibodies in complex with the envelope protein of Zika virus reveals the details of a conserved epitope, which is also the site of interaction of the envelope protein dimer with the precursor membrane (prM) protein during virus maturation. Comparison of the Zika and dengue virus immunocomplexes provides a lead for rational, epitope-focused design of a universal vaccine capable of eliciting potent cross-neutralizing antibodies to protect simultaneously against both Zika and dengue virus infections.
机译:寨卡病毒是黄病毒属的一种成员,直到最近的爆发才与人类的严重疾病有关,当时它与巴西新生儿的小头畸形和法属波利尼西亚的成年人的格林巴利综合症有关。 Zika病毒与登革热病毒有关,在这里我们报道了针对从登革热病毒患者中分离的构象表位的抗体亚群也可以有效地中和Zika病毒。这些抗体中的两种与Zika病毒包膜蛋白复合的晶体结构揭示了保守表位的细节,这也是在病毒成熟过程中包膜蛋白二聚体与前体膜(prM)蛋白相互作用的位点。寨卡病毒和登革热病毒免疫复合物的比较为通用疫苗的合理,以抗原决定簇为重点的设计提供了线索,该通用疫苗能够引发有效的交叉中和抗体,从而同时针对寨卡病毒和登革热病毒感染提供保护。

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  • 来源
    《Nature》 |2016年第7614期|48-53|共6页
  • 作者单位

    Inst Pasteur, Unite Virol Struct, Dept Virol, F-75724 Paris 15, France|CNRS, UMR Virol 3569, F-75724 Paris 15, France;

    Imperial Coll London, Dept Med, Div Immunol & Inflammat, Hammersmith Campus, London W12 0NN, England;

    Inst Pasteur, Unite Virol Struct, Dept Virol, F-75724 Paris 15, France|CNRS, UMR Virol 3569, F-75724 Paris 15, France;

    Inst Pasteur, Unite Virol Struct, Dept Virol, F-75724 Paris 15, France|CNRS, UMR Virol 3569, F-75724 Paris 15, France;

    Med Univ Vienna, Dept Virol, Kinderspitalgasse 15, A-1095 Vienna, Austria;

    Inst Pasteur, Unite Virol Struct, Dept Virol, F-75724 Paris 15, France|CNRS, UMR Virol 3569, F-75724 Paris 15, France;

    Inst Pasteur, Unite Genet Fonct Malad Infect, Dept Genomes & Genet, F-75724 Paris 15, France|CNRS, URA 3012, F-75724 Paris 15, France;

    Inst Pasteur, Unite Genet Fonct Malad Infect, Dept Genomes & Genet, F-75724 Paris 15, France|CNRS, URA 3012, F-75724 Paris 15, France;

    Inst Louis Malarde, Unit Emerging Infect Dis, Papeete 98713, Tahiti, Fr Polynesia;

    Inst Pasteur, Plateforme Cristallog CiTech, Dept Biol Struct & Chim, F-75724 Paris 15, France|CNRS, UMR 3528, F-75724 Paris 15, France;

    CNRS, UMR 3528, F-75724 Paris 15, France|Inst Pasteur, Plateforme Biophys Macromol & Leurs Interact, CiTech, Dept Biol Struct & Chim, F-75724 Paris 15, France;

    Med Univ Vienna, Dept Virol, Kinderspitalgasse 15, A-1095 Vienna, Austria;

    Imperial Coll London, Dept Med, Div Immunol & Inflammat, Hammersmith Campus, London W12 0NN, England|Mahidol Univ, Siriraj Hosp, Dengue Hemorrhag Fever Res Unit, Off Res & Dev,Fac Med, Bangkok 10700, Thailand;

    Med Univ Vienna, Dept Virol, Kinderspitalgasse 15, A-1095 Vienna, Austria;

    Imperial Coll London, Dept Med, Div Immunol & Inflammat, Hammersmith Campus, London W12 0NN, England;

    Inst Pasteur, Unite Virol Struct, Dept Virol, F-75724 Paris 15, France|CNRS, UMR Virol 3569, F-75724 Paris 15, France;

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