Identification of a New Broadly Cross-reactive Epitope within Domain III of the Duck Tembusu Virus E Protein.
In 2010, a pathogenic flavivirus termed duck Tembusu virus (DTMUV) caused widespread outbreak of egg-drop syndrome in domesticated ducks in China. Although the glycoprotein E of DTMUV is an important structural component of the virus, the B-cell epitopes of this protein remains uncharacterized. Using phage display and mutagenesis, we identified a minimal B-cell epitope,374EXE/DPPFG380, that mediates binding to a nonneutralizing monoclonal antibody. DTMUV-positive duck serum reacted with the epitope, and amino acid substitutions revealed the specific amino acids that are essential for antibody binding. Dot-blot assays of various flavivirus-positive sera indicated that EXE/DPPFG is a cross-reactive epitope in most flaviviruses, including Zika, West Nile, Yellow fever, dengue, and Japanese encephalitis viruses. These findings indicate that the epitope sequence is conserved among many strains of mosquito-borne flavivirus. Protein structure modeling revealed that the epitope is located in domain III of the DTMUV E protein. Together, these results provide new insights on the broad cross-reactivity of a B-cell binding site of the E protein of flaviviruses, which can be exploited as a diagnostic or therapeutic target for identifying, studying, or treating DTMUV and other flavivirus infections.
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, 150001, China.
Chenxi
C
Li
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, 150001, China.
Xiaofei
X
Bai
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, 150001, China.
Runze
R
Meng
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, 150001, China.
Wulin
W
Shaozhou
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, 150001, China.
Qingshan
Q
Zhang
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, 150001, China.
Ronghong
R
Hua
Institute of Genomics and Bioinformatics, National Chung Hsing University. Taiwan.
Jyung-Hurng
JH
Liu
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, 150001, China.
Ming
M
Liu
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, 150001, China.
Yun
Y
Zhang
D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites; D004372:Ducks / Q000821:virology*; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte / Q000235:genetics* / Q000378:metabolism; D005416:Flavivirus / Q000235:genetics / Q000378:metabolism*; D018177:Flavivirus Infections / Q000821:virology; D008958:Models, Molecular; D009154:Mutation; D019151:Peptide Library; D011201:Poultry Diseases / Q000821:virology; D000072417:Protein Domains; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000235:genetics
D018985:Epitopes, B-Lymphocyte; D019151:Peptide Library; D014759:Viral Envelope Proteins