Comparative Study of Envelope Proteins of Dengue Virus of All Four Serotypes Isolated In India

Abstract

Dengue virus infections spread mainly by the Aedes mosquitoes, affect 50 to 100 million people annually, of which a small percentage can suffer severe dengue hemorrhagic fever that can be fatal, and dengue fever in epidemic form has been affecting mainly the tropical countries. The tragedy is compounded by the fact that there are as yet no drugs or vaccines to treat the disease or act as preventives. Also, dengue virus belongs to the Flavivirus family, which also includes the latest Zika virus that is also spread by the same vector. The impact of such viruses makes it important to understand and characterize them, especially their surface proteins which continue to remain the first point of attack for drug and prophylaxis design. In this paper we consider the dengue surface situated envelope protein for all dengue serotypes from India to characterize the sequences and determine their similarities and dissimilarities with a view to assist in monitoring viral changes and in design of drugs and vaccines. We found the nucleotide sequences of the envelope genes of all four dengue serotypes to be very similar at the 3´-end, while there are slightly more differences near the 5´-end where the presence of the glycosilation site is known to be accompanied by large variability in the amino acid sequences. Phylogenetic analysis showed that the dengue type 4 (DENV4) is cladistically slightly removed compared to the other three dengue serotypes (DENV1, DENV3 and DENV2). The codon usage profiles show differences in codon usage biases between various serotypes. All four serotypes exhibit similar transition-transversion ratios and amino acid usage patterns; hydropathy indexes show small differences between DENV1, 4 and DENV2, 3. Our analyses identified three surface exposed regions in the protein sequences that are common to all four serotypes, which may be of interest in vaccine design.