Phylogenetic and Conservational Analyses of Dengue Non-Structural Protein 1

Abstract

The variability in the host immune responses against infections by different strains of Dengue virus (DENV), due to their sequence heterogeinity, is a huge obstacle in disease management and development of an effective vaccine. In depth understanding of genetic diversity among different serotypes and strains is therefore an important factor to manage the disease. This study is an attempt to analyze the phylogenetic diversity of dengue Non-Structural protein 1 (NS1), which has a significant functional role in dengue pathogenesis. Fifty sequences of NS1, each from the four dengue serotypes, Japanese Encephalitic Virus (JEV) and West Nile Virus (WNV) were obtained from NCBI Genebank, were phylogenetically aligned on MEGA6. The level of conservation of the sequences was analyzed by IEDB analysis tools and WebLogo. The sequences from each strain were selected representing a broad time span and multiple regions of the world. In the phylogenetic tree, strains of each DENV serotype were grouped into four main geographical locations, Africa, South America, South East Asia and China. DENV 1 and 3 were phylogenetically closer among the four serotypes. They further showed more than 80% conservation between each other. DENV 4 showed a higher deviation from other three serotypes. Strains from DENV3 showed high level of sequence conservation, while it was highly variable within DENV 4. Dengue group showed a conservation level of 50% in NS1 protein with JEV and WNV. However, the carboxy terminal region of the protein (271-352aa) appeared more conserved across different flavivirus groups, showing a conservation level of more than 70%. The understanding of genetic variability or similarity among and within the serotypes of dengue virus would provide insight into better management of the disease.