Bioinformatics analysis and characteristics of envelop glycoprotein E epitopes of dengue virus

Hua Zhong, Wei Zhao, Liang Peng, Shan-Feng Li, Hong Cao

Department of Microbiology, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong 510515, China.
Department of Microbiology, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong 510515, China..

DOI: 10.4236/jbise.2009.22022                

Abstract

The major envelope glycoprotein E of dengue (DEN) virus 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 un-clear where the well-defined B-cell epitopes for glycoprotein E which induce the neutralizing an-tibodies locates. Thus, in order to characterize the role of glycoprotein E in the pathogenesis of dengue virus infection, we first used network servers (http://bio.dfci. harvard.edu/Tools/ & http://www. imtech. res. in) to predict and analyze the well defined B-cell and T-cell epitopes of the glycoprotein of the DEN-1 HAWAII strain. Then based on the highly conserved envelop glyco-protein amino acids, the hydrophilicity, antigenic-ity, accessibility and flexibility of envelop glyco-protein E were further predicted by using Biotic softwares (DNASTAR) and network servers (http://bio. dfci.harvard.edu/Tools/), the secondary structure was putatively obtained. In our study, the sequence at 281-295 amino acid (aa) for den-gue 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 epi-topes by using multiple parameters and different analysis softwares, respectively. Two epitopes of DEN-2 and one of DEN-1 locate on the domain Ш and domainⅡ of the protein E, respectively. Sub-sequently, further studies will be carried out to examine the antigenicity and protection of the synthetic peptides with higher scores in the av-erage antigen index (AI) and better hydrophilic properties determined by our data.

Keywords

Dengue Virus, Glycoprotein E, Epitope, Bioinformatics

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	T. Monath.(1994) Dengue: the risk to developed and developing countries. Proc Natl Acad Sci USA 91, 2395-2400.
[2]	R. J. Kuhn, W. Zhang, M. G. Rossmann. (2002) Structure of dengue virus: implications for flavivirus organization, matu--ration, and fusion. Cell 108, 717-725.
[3]	E. A. Henchal, J. R. Putnak. (1990) The dengue viruses. Clin Microbiol Rev 3, 376-396.
[4]	C. M. Rice, B. N. Fields, D. M. Knipe, P. M. Howley. (1996)Flaviviridae: the viruses and their replication. Virology 3, 931-959.
[5]	J. T. Roehrig. Immunochemistry of the dengue viruses, 199-219 In: D. J. Gubler and G. Kuno (eds), Dengue and dengue hemorrhagic fever. CAB International, New York, N. Y. 1997.
[6]	G. J. Chang, Molecular biology of dengue viruses, 175-198 In: D. J. Gubler, G. Kuno (eds.), Dengue and Dengue Hemorrhagic Fever. CAB International, London, 1997.
[7]	A. S. Kolaskar, P. C. Tongaonkar. (1990) A semi-empirical method for prediction of antigenic determinants on protein anti-gens, FEBS Lett 276, 172-174.
[8]	M. Levitt, J. Greer. (1977) Automatic identification of secondary structure in globular proteins. J Mol Biol 114, 181-239.
[9]	J Cheng. (2008) A multi-template combination algorithm for protein comparative modeling. BMC Structural Biology 8, 18-36.
[10]	G. Deleage, B. Roux. (1987) An algorithm for protein secondary structure prediction based on class prediction. Protein Eng 1, 289-294.
[11]	J. Martin, J. F. Gibrat, F. Rodolphe. (2006) Analysis of an opti-mal hidden Markov model for secondary structure prediction. BMC Structural Biology 6, 25-45.
[12]	E. A. Emini, J. V. Hughes, D. S. Peflow. (1985) Induction of hepa-titis A vires-neutralizing antibody by a vires-specific syn-thetic peptide. J Virol 55,836-839.
[13]	P. A. Karplus, G. Schultz. (1985) Prediction of chain flexibility in proteins. Naturwissenschaften 72, 212-213.
[14]	Y. Modis, S. Ogata, D. Clements. (2003) A ligand-binding pockets in the dengue virus envelop glycoprotein. Science 100, 6986-6991.