Complete genome sequencing and evolutionary phylogeography analysis of Indian isolates of Dengue virus type 1

Dengue is now hyper-endemic in most parts of south and southeast Asia including India. The northern India particularly national capital New Delhi witnessed major Dengue outbreaks with Dengue virus type 1 (DENV-1) as the dominant serotype since last five years. This study was initiated to decipher the complete genome information of recently circulating DENV-1 (2009-2011) along with the prototype Indian DENV-1, isolated in 1956. Further extensive ML phylogenetic and Bayesian phylogeography analysis was carried out to investigate the evolution of this virus and understand its spatiotemporal diffusion across the globe. The complete genome analysis revealed deletion of a unique 21-nucleotide stretch in the 3' un-translated region of recent Indian DENV-1. The north Indian DENV-1 revealed up to 5.2% nucleotide sequence difference compared to recent isolates from southern India. Selection pressure analysis revealed positive selection in few amino acid sites of both structural and non-structural proteins. The molecular phylogeny classified the Indian DENV-1 into genotype III, which is also known as cosmopolitan genotype. The northern and southern Indian DENV-1 were grouped into distinct clades. The molecular clock analysis estimated a mean evolutionary rate of 7.08×10(-4) substitutions/site/year for cosmopolitan genotype. The phylogeography analysis revealed that the cosmopolitan genotype DENV-1 originated ∼1938 in India and subsequently spread globally. The diffusion of virus from India to Caribbean and South America was confirmed through SPREAD analysis. This study also confirmed the temporal displacement of different clades of DENV-1 in India over last five decades.