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


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.

SUBMITTER: Ji GH 

PROVIDER: S-EPMC4592203 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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

Ji Guang-Hui GH   Deng Yong-Qiang YQ   Yu Xiao-Jie XJ   Jiang Tao T   Wang Hua-Jing HJ   Shi Xin X   Zhang Da-Peng DP   Li Xiao-Feng XF   Zhu Shun-Ya SY   Zhao Hui H   Dai Jian-Xin JX   Qin Cheng-Feng CF   Guo Ya-Jun YJ  

PloS one 20151002 10


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-direc  ...[more]

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