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包膜蛋白结构域III上一种新型登革4型病毒特异性中和表位的鉴定

Characterization of a Novel Dengue Serotype 4 Virus-Specific Neutralizing Epitope on the Envelope Protein Domain III.

作者信息

Ji Guang-Hui, Deng Yong-Qiang, Yu Xiao-Jie, Jiang Tao, Wang Hua-Jing, Shi Xin, Zhang Da-Peng, Li Xiao-Feng, Zhu Shun-Ya, Zhao Hui, Dai Jian-Xin, Qin Cheng-Feng, Guo Ya-Jun

机构信息

Department of Traditional Chinese Medicine, Navy General Hospital, Beijing, China; International Joint Cancer Institute, Second Military Medical University, Shanghai, China.

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.

出版信息

PLoS One. 2015 Oct 2;10(10):e0139741. doi: 10.1371/journal.pone.0139741. eCollection 2015.

DOI:10.1371/journal.pone.0139741
PMID:26430770
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4592203/
Abstract

The dengue virus (DENV) envelope protein domain III (ED3) has been suggested to contain receptor recognition sites and the critical neutralizing epitopes. Up to date, relatively little work has been done on fine mapping of neutralizing epitopes on ED3 for DENV4. In this study, a novel mouse type-specific neutralizing antibody 1G6 against DENV4 was obtained with both prophylactic and therapeutic effects. The epitope was mapped to residues 387-390 of DENV4 envelope protein. Furthermore, site-directed mutagenesis assay identified two critical residues (T388 and H390). The epitope is variable among different DENV serotypes but is highly conserved among four DENV4 genotypes. Affinity measurement showed that naturally occurring variations in ED3 outside the epitope region did not alter the binding of mAb 1G6. These findings expand our understanding of the interactions between neutralizing antibodies and the DENV4 and may be valuable for rational design of DENV vaccines and antiviral drugs.

摘要

登革病毒（DENV）包膜蛋白结构域III（ED3）被认为含有受体识别位点和关键的中和表位。迄今为止，针对DENV4的ED3上中和表位的精细定位所做的工作相对较少。在本研究中，获得了一种新型的针对DENV4的小鼠型特异性中和抗体1G6，它具有预防和治疗作用。该表位被定位到DENV4包膜蛋白的387 - 390位氨基酸残基。此外，定点诱变分析确定了两个关键残基（T388和H390）。该表位在不同的DENV血清型之间存在差异，但在四种DENV4基因型中高度保守。亲和力测量表明，表位区域外ED3的天然存在的变异不会改变单克隆抗体1G6的结合。这些发现扩展了我们对中和抗体与DENV4之间相互作用的理解，可能对DENV疫苗和抗病毒药物的合理设计有价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/137b/4592203/e20b9b78b4f2/pone.0139741.g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/137b/4592203/e20b9b78b4f2/pone.0139741.g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/137b/4592203/e20b9b78b4f2/pone.0139741.g008.jpg

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Dengue serotype cross-reactive, anti-e protein antibodies confound specific immune memory for 1 year after infection.登革血清型交叉反应性、抗 E 蛋白抗体在感染后 1 年内混淆特异性免疫记忆。
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