Bioinformatics Prediction and Characteristics of B Cell Epitopes of Envelop Glycoprotein E of Dengue Virus

摘要

Dengue (DEN) virus, a member of the flavivirus familiy, is an emerging global threat. The major envelope glycoprotein E plays a central role in the biology of flaviviruses. It is capable of inducing a protective immune response in vivo and responsible for the viral binding to the cellular receptor. The crystal structures of glycoprotein E ectodomains have already been determined. However, it is still unclear where the well-defined B-cell epitopes for glycoprotein E which induce the neutralizing antibodies locates. Thus, in order to characterize the role of glycoprotein E in the pathogenesis of dengue virus infection, we used bioinformatics and molecular approaches to predict and analyze its B-cell antigen epitopes. Based on the highly conserved envelop glycoprotein amino acids, the hydrophilicity, antigenicity, accessibility and flexibility of envelop glycoprotein E were further predicted by using Biotic softwares (DNASTAR) and network servers (http:// bio. dfci. harvard.edu/Tools/), then the secondary structure was putatively obtained. In our study, the sequence at 281 ~ 295 amino acid (aa) for dengue virus type 1 HAWAII strain and the sequence at 345 - 359, 383 ~ 397 for dengue virus type 2 NGC strain were predicted as the more prevalent epitopes by using multiple parameters and different analysis softwares, respectively. The sequences selected not only have higher scores in the average antigen index (AI), which could predict the antigen epitope of envelop glycoprotein E, but also showed better hydrophilic properties. Two epitopes of DEN-2 and one of DEN-1 locate on the domain III and domain II of the protein E, respectively. The domain III has been hypothesized to contain multiple type- and subtype-specific epitopes eliciting only virus-neutralizing monoclonal antibodies while the domain II is involved in virus-mediated membrane fusion, and contains many cross-reactive epitopes eliciting neutralizing and non-neutralizing monoclonal antibodies. Subsequently, further studies will be carried out to examine the antigenicity and protection of synthetic peptides determined by our data.