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

被引:9
作者
Ji, Guang-Hui [1 ,2 ]
Deng, Yong-Qiang [3 ]
Yu, Xiao-Jie [2 ]
Jiang, Tao [3 ]
Wang, Hua-Jing [2 ]
Shi, Xin [2 ]
Zhang, Da-Peng [2 ]
Li, Xiao-Feng [3 ]
Zhu, Shun-Ya [3 ]
Zhao, Hui [3 ]
Dai, Jian-Xin [2 ]
Qin, Cheng-Feng [3 ]
Guo, Ya-Jun [2 ]
机构
[1] Navy Gen Hosp, Dept Tradit Chinese Med, Beijing, Peoples R China
[2] Second Mil Med Univ, Int Joint Canc Inst, Shanghai, Peoples R China
[3] Beijing Inst Microbiol & Epidemiol, State Key Lab Pathogen & Biosecur, Beijing, Peoples R China
基金
中国国家自然科学基金;
关键词
WEST-NILE-VIRUS; MONOCLONAL-ANTIBODIES; STRUCTURAL BASIS; E-GLYCOPROTEIN; FUSION-LOOP; TYPE-2; PROTECTION; INFECTION; DETERMINANTS; THAILAND;
D O I
10.1371/journal.pone.0139741
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 387390 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.
引用
收藏
页数:18
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