• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

黄病毒颗粒表面的表位排列有助于 Mab C10 对寨卡病毒和登革热病毒产生非凡的广谱中和作用。

The epitope arrangement on flavivirus particles contributes to Mab C10's extraordinary neutralization breadth across Zika and dengue viruses.

机构信息

Institut Pasteur, Université de Paris, CNRS UMR3569, Unité de Virologie Structurale, 75015 Paris, France.

Institut Pasteur, Université de Paris, CNRS UMR3569, Unité de Virologie Structurale, 75015 Paris, France; Interdisciplinary Center for Brain Information, the Brain Cognition and Brain Disease Institute, Faculty of Life and Health Sciences, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, Guangdong 518055, China.

出版信息

Cell. 2021 Dec 9;184(25):6052-6066.e18. doi: 10.1016/j.cell.2021.11.010. Epub 2021 Nov 30.

DOI:
10.1016/j.cell.2021.11.010
PMID:34852239
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8724787/
Abstract

The human monoclonal antibody C10 exhibits extraordinary cross-reactivity, potently neutralizing Zika virus (ZIKV) and the four serotypes of dengue virus (DENV1-DENV4). Here we describe a comparative structure-function analysis of C10 bound to the envelope (E) protein dimers of the five viruses it neutralizes. We demonstrate that the C10 Fab has high affinity for ZIKV and DENV1 but not for DENV2, DENV3, and DENV4. We further show that the C10 interaction with the latter viruses requires an E protein conformational landscape that limits binding to only one of the three independent epitopes per virion. This limited affinity is nevertheless counterbalanced by the particle's icosahedral organization, which allows two different dimers to be reached by both Fab arms of a C10 immunoglobulin. The epitopes' geometric distribution thus confers C10 its exceptional neutralization breadth. Our results highlight the importance not only of paratope/epitope complementarity but also the topological distribution for epitope-focused vaccine design.

摘要

人源单克隆抗体 C10 表现出非凡的交叉反应性，能够有效中和寨卡病毒（ZIKV）和四种血清型登革热病毒（DENV1-DENV4）。在这里，我们描述了 C10 与它中和的五种病毒的包膜（E）蛋白二聚体结合的比较结构功能分析。我们证明 C10 Fab 对 ZIKV 和 DENV1 具有高亲和力，但对 DENV2、DENV3 和 DENV4 没有亲和力。我们进一步表明，C10 与后两种病毒的相互作用需要一种 E 蛋白构象景观，这种构象景观限制了与每个病毒粒子上三个独立表位中的一个结合。尽管亲和力有限，但该粒子的二十面体组织平衡了这一点，允许 C10 免疫球蛋白的两个 Fab 臂到达两个不同的二聚体。因此，表位的几何分布赋予了 C10 异常广泛的中和能力。我们的研究结果不仅强调了互补位/表位互补性的重要性，还强调了表位聚焦疫苗设计的拓扑分布的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/126a/8724787/f97e6b8dadc9/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/126a/8724787/24d0d6480b48/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/126a/8724787/2b73c83ae004/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/126a/8724787/fa94f556538e/figs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/126a/8724787/a6f5c2675a3f/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/126a/8724787/74b95755df7a/figs2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/126a/8724787/0f602d381205/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/126a/8724787/0cbfde38ff63/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/126a/8724787/4aaef7538855/figs3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/126a/8724787/f935bbf24024/figs4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/126a/8724787/f86a4ebce220/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/126a/8724787/a5fbbf0bde04/figs5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/126a/8724787/d5418e0e7a05/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/126a/8724787/d6b1e1de6fe3/figs6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/126a/8724787/6dd06a0b5c9a/figs7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/126a/8724787/f97e6b8dadc9/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/126a/8724787/24d0d6480b48/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/126a/8724787/2b73c83ae004/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/126a/8724787/fa94f556538e/figs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/126a/8724787/a6f5c2675a3f/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/126a/8724787/74b95755df7a/figs2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/126a/8724787/0f602d381205/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/126a/8724787/0cbfde38ff63/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/126a/8724787/4aaef7538855/figs3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/126a/8724787/f935bbf24024/figs4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/126a/8724787/f86a4ebce220/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/126a/8724787/a5fbbf0bde04/figs5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/126a/8724787/d5418e0e7a05/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/126a/8724787/d6b1e1de6fe3/figs6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/126a/8724787/6dd06a0b5c9a/figs7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/126a/8724787/f97e6b8dadc9/gr7.jpg

相似文献

1
The epitope arrangement on flavivirus particles contributes to Mab C10's extraordinary neutralization breadth across Zika and dengue viruses.黄病毒颗粒表面的表位排列有助于 Mab C10 对寨卡病毒和登革热病毒产生非凡的广谱中和作用。
Cell. 2021 Dec 9;184(25):6052-6066.e18. doi: 10.1016/j.cell.2021.11.010. Epub 2021 Nov 30.
2
Human antibody C10 neutralizes by diminishing Zika but enhancing dengue virus dynamics.人源抗体 C10 通过减少 Zika 病毒而增强登革热病毒动力学。
Cell. 2021 Dec 9;184(25):6067-6080.e13. doi: 10.1016/j.cell.2021.11.009. Epub 2021 Nov 30.
3
Mechanism of differential Zika and dengue virus neutralization by a public antibody lineage targeting the DIII lateral ridge.靶向 III 区侧脊的公共抗体谱系对寨卡病毒和登革热病毒的差异化中和作用机制。
J Exp Med. 2020 Feb 3;217(2). doi: 10.1084/jem.20191792.
4
Structural Basis of Zika Virus Specific Neutralization in Subsequent Flavivirus Infections.寨卡病毒特异性中和的结构基础在后续黄病毒感染中的作用。
Viruses. 2020 Nov 24;12(12):1346. doi: 10.3390/v12121346.
5
Dengue Virus Envelope Dimer Epitope Monoclonal Antibodies Isolated from Dengue Patients Are Protective against Zika Virus.从登革热患者中分离出的登革病毒包膜二聚体表位单克隆抗体对寨卡病毒具有保护作用。
mBio. 2016 Jul 19;7(4):e01123-16. doi: 10.1128/mBio.01123-16.
6
Structural basis of potent Zika-dengue virus antibody cross-neutralization.强效寨卡-登革热病毒抗体交叉中和的结构基础。
Nature. 2016 Aug 4;536(7614):48-53. doi: 10.1038/nature18938. Epub 2016 Jun 23.
7
Human antibodies to the dengue virus E-dimer epitope have therapeutic activity against Zika virus infection.针对登革病毒E二聚体表位的人源抗体对寨卡病毒感染具有治疗活性。
Nat Immunol. 2017 Nov;18(11):1261-1269. doi: 10.1038/ni.3849. Epub 2017 Sep 25.
8
Human dengue virus serotype 2 neutralizing antibodies target two distinct quaternary epitopes.人类登革热病毒血清型 2 中和抗体靶向两个不同的四级表位。
PLoS Pathog. 2018 Feb 26;14(2):e1006934. doi: 10.1371/journal.ppat.1006934. eCollection 2018 Feb.
9
Dengue and Zika Virus Domain III-Flagellin Fusion and Glycan-Masking E Antigen for Prime-Boost Immunization.登革热和 Zika 病毒结构域 III-鞭毛蛋白融合和糖基掩蔽 E 抗原用于初次-加强免疫。
Theranostics. 2019 Jul 9;9(16):4811-4826. doi: 10.7150/thno.35919. eCollection 2019.
10
An Envelope-Modified Tetravalent Dengue Virus-Like-Particle Vaccine Has Implications for Flavivirus Vaccine Design.一种经包膜修饰的四价登革病毒样颗粒疫苗对黄病毒疫苗设计具有启示意义。
J Virol. 2017 Nov 14;91(23). doi: 10.1128/JVI.01181-17. Print 2017 Dec 1.

引用本文的文献

1
Structural elucidation of a unique binding mode by an intact alphavirus human IgG molecule to a quaternary epitope.完整的甲病毒人IgG分子与四级表位独特结合模式的结构解析
Nat Commun. 2025 Aug 19;16(1):7716. doi: 10.1038/s41467-025-60505-x.
2
Insights into the Landscape of Alphavirus Receptor and Antibody Interactions.深入了解甲病毒受体与抗体相互作用的格局
Viruses. 2025 Jul 21;17(7):1019. doi: 10.3390/v17071019.
3
Protective envelope dimer epitope-like antibodies are elicited against dengue virus in children after infection and vaccination.

本文引用的文献

1
Human antibody C10 neutralizes by diminishing Zika but enhancing dengue virus dynamics.人源抗体 C10 通过减少 Zika 病毒而增强登革热病毒动力学。
Cell. 2021 Dec 9;184(25):6067-6080.e13. doi: 10.1016/j.cell.2021.11.009. Epub 2021 Nov 30.
2
A unified route for flavivirus structures uncovers essential pocket factors conserved across pathogenic viruses.一种统一的黄病毒结构途径揭示了在致病性病毒中保守的关键口袋因子。
Nat Commun. 2021 Jun 1;12(1):3266. doi: 10.1038/s41467-021-22773-1.
3
Ethics of a partially effective dengue vaccine: Lessons from the Philippines.
感染和接种疫苗后，儿童体内会产生针对登革病毒的保护性包膜二聚体表位样抗体。
Sci Transl Med. 2025 Jul 23;17(808):eadq0571. doi: 10.1126/scitranslmed.adq0571.
4
Machine learning-assisted multi-dimensional transcriptomic analysis of cytoskeleton-related molecules and their relationship with prognosis in hepatocellular carcinoma.机器学习辅助的肝细胞癌细胞骨架相关分子的多维度转录组分析及其与预后的关系
Sci Rep. 2025 Jul 3;15(1):23832. doi: 10.1038/s41598-025-10056-4.
5
Structural basis for antibody cross-neutralization of Dengue and Zika viruses.抗体对登革热病毒和寨卡病毒交叉中和作用的结构基础
bioRxiv. 2025 Jun 21:2025.06.05.658091. doi: 10.1101/2025.06.05.658091.
6
Heterologous prime-boost Zika virus vaccination induces comprehensive humoral and cellular immunity in mouse models.异源初免-加强寨卡病毒疫苗接种在小鼠模型中诱导全面的体液免疫和细胞免疫。
Front Immunol. 2025 Apr 25;16:1578427. doi: 10.3389/fimmu.2025.1578427. eCollection 2025.
7
Toward a deeper understanding of dengue: novel method for quantification and isolation of envelope protein epitope-specific antibodies.迈向对登革热的更深入理解：定量和分离包膜蛋白表位特异性抗体的新方法。
mSphere. 2025 May 27;10(5):e0096124. doi: 10.1128/msphere.00961-24. Epub 2025 Apr 11.
8
In Silico Evaluation of Potential Hit Molecules Against Multiple Serotypes of Dengue Virus Envelope Glycoprotein.针对登革病毒包膜糖蛋白多种血清型的潜在活性分子的计算机模拟评估
Molecules. 2025 Mar 12;30(6):1268. doi: 10.3390/molecules30061268.
9
Zika virus vaccines and monoclonal antibodies: a priority agenda for research and development.寨卡病毒疫苗和单克隆抗体：研发的优先议程
Lancet Infect Dis. 2025 Jul;25(7):e402-e415. doi: 10.1016/S1473-3099(24)00750-3. Epub 2025 Feb 27.
10
Animal Models, Therapeutics, and Vaccine Approaches to Emerging and Re-Emerging Flaviviruses.针对新出现和再次出现的黄病毒的动物模型、治疗方法及疫苗策略
Viruses. 2024 Dec 24;17(1):1. doi: 10.3390/v17010001.
部分有效的登革热疫苗的伦理问题：来自菲律宾的教训。
Vaccine. 2020 Jul 31;38(35):5572-5576. doi: 10.1016/j.vaccine.2020.06.079. Epub 2020 Jul 10.
4
Long-term circulation of Zika virus in Thailand: an observational study.泰国寨卡病毒的长期循环：一项观察性研究。
Lancet Infect Dis. 2019 Apr;19(4):439-446. doi: 10.1016/S1473-3099(18)30718-7. Epub 2019 Feb 27.
5
A Combination of Two Human Monoclonal Antibodies Prevents Zika Virus Escape Mutations in Non-human Primates.两种人源单克隆抗体的联合使用可防止寨卡病毒在非人类灵长类动物中发生逃逸突变。
Cell Rep. 2018 Nov 6;25(6):1385-1394.e7. doi: 10.1016/j.celrep.2018.10.031.
6
The emergence of Zika virus and its new clinical syndromes.寨卡病毒的出现及其新的临床综合征。
Nature. 2018 Aug;560(7720):573-581. doi: 10.1038/s41586-018-0446-y. Epub 2018 Aug 29.
7
Refinement and Analysis of the Mature Zika Virus Cryo-EM Structure at 3.1 Å Resolution. refinement and analysis of the mature Zika virus cryo-EM structure at 3.1 Å resolution.
Structure. 2018 Sep 4;26(9):1169-1177.e3. doi: 10.1016/j.str.2018.05.006. Epub 2018 Jun 26.
8
MolProbity: More and better reference data for improved all-atom structure validation.MolProbity：用于改进全原子结构验证的更多更好的参考数据。
Protein Sci. 2018 Jan;27(1):293-315. doi: 10.1002/pro.3330. Epub 2017 Nov 27.
9
A pUL25 dimer interfaces the pseudorabies virus capsid and tegument.pUL25二聚体连接伪狂犬病病毒的衣壳和被膜。
J Gen Virol. 2017 Nov;98(11):2837-2849. doi: 10.1099/jgv.0.000903. Epub 2017 Oct 16.
10
Zika virus activates de novo and cross-reactive memory B cell responses in dengue-experienced donors.寨卡病毒在曾感染过登革热的献血者体内激活了从头产生的和交叉反应性记忆B细胞反应。
Sci Immunol. 2017 Aug 18;2(14). doi: 10.1126/sciimmunol.aan6809.