title: 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.
authors.affiliation: Department of Traditional Chinese Medicine, Navy General Hospital, Beijing, China; International Joint Cancer Institute, Second Military Medical University, Shanghai, China.
authors.forename: Guang-Hui
authors.initials: GH
authors.lastname: Ji
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Yong-Qiang
authors.initials: YQ
authors.lastname: Deng
authors.affiliation: International Joint Cancer Institute, Second Military Medical University, Shanghai, China.
authors.forename: Xiao-Jie
authors.initials: XJ
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.affiliation: International Joint Cancer Institute, Second Military Medical University, Shanghai, China.
authors.forename: Hua-Jing
authors.initials: HJ
authors.lastname: Wang
authors.affiliation: International Joint Cancer Institute, Second Military Medical University, Shanghai, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Shi
authors.affiliation: International Joint Cancer Institute, Second Military Medical University, Shanghai, China.
authors.forename: Da-Peng
authors.initials: DP
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Li
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Shun-Ya
authors.initials: SY
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.affiliation: International Joint Cancer Institute, Second Military Medical University, Shanghai, China.
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Dai
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Cheng-Feng
authors.initials: CF
authors.lastname: Qin
authors.affiliation: International Joint Cancer Institute, Second Military Medical University, Shanghai, China.
authors.forename: Ya-Jun
authors.initials: YJ
authors.lastname: Guo
mesh_terms: D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003716:Dengue Virus / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D009500:Neutralization Tests; D014759:Viral Envelope Proteins / Q000276:immunology
chemical_list: D000939:Epitopes; D014759:Viral Envelope Proteins