Abstract
BackgroundPattern of Dengue periodic epidemics through the years along with sporadic cases of Dengue hemorrhagic fever followed by a severe 2011 epidemic of Dengue fever in Pakistan make Pakistan a Dengue endemic country. To study the entry and evolution of dengue virus serotype 2 (DENV-2) in Pakistan, we sequenced three full length genomes and 24 complete envelope sequences of DENV-2 from the years 2010, 2011 and 2013 collected from Punjab province of Pakistan.MethodsPhylogenetic and Bayesian phylogeographic analyses was applied to three full genome sequences as well as 24 envelope sequences to study the spatiotemporal dynamics of DENV-2 in Pakistan.ResultsMost of the DENV-2 viruses from the years 2008 to 2013 formed a monophyletic Pakistani clade in IVb sublineage of cosmopolitan genotype except one 2008 DENV-2 strain. Phylogeographic analysis revealed that this 2008 DENV-2 strain was rooted to India 25.4 years ago with a location probability of 0.88. However Pakistani clade rooted back to Sri Lanka 12.6 years ago with a location probability of 0.57.ConclusionDENV-2 genotype IV was introduced in Pakistan in two time events. First event was introduction from India to Pakistan in the late 1980s (around 1986), and second event was introduction from Sri Lanka to Pakistan around 2000. The later introduction event was responsible for major outbreaks in the Punjab region of Pakistan, including major 2011 outbreak. After the second Introduction event, DENV-2 circulated locally in the region forming a distinct Sublineage within the IVb cosmopolitan genotype of DENV-2.Electronic supplementary materialThe online version of this article (doi:10.1186/s12985-015-0371-8) contains supplementary material, which is available to authorized users.
Highlights
Dengue virus (DENV) having four serotypes (DENV-1 through 4) is a mosquito borne Flavivirus that has been found in more than 100 countries with estimated 50-100 million dengue infection cases each year [1]
Phylogenetic analysis of complete genome sequences of Pakistani dengue virus serotype 2 (DENV-2) isolates has further added that it belonged to Indian subcontinent lineage of genotype IV or cosmopolitan genotype [13]
Evolutionary divergence of DENV-2 as analyzed from phylogenetic trees generated from full length as well as envelope sequences grouped DENV-2 sequences in five genotypes (Fig. 1 and 2)
Summary
Dengue virus (DENV) having four serotypes (DENV-1 through 4) is a mosquito borne Flavivirus that has been found in more than 100 countries with estimated 50-100 million dengue infection cases each year [1]. Phylogenetic analysis of partial DENV-2 sequences has revealed that genotype IV or cosmopolitan genotype of DENV-2 is circulating in Pakistan [10]. Phylogenetic analysis of complete genome sequences of Pakistani DENV-2 isolates has further added that it belonged to Indian subcontinent lineage of genotype IV or cosmopolitan genotype [13]. To study the entry and evolution of dengue virus serotype 2 (DENV-2) in Pakistan, we sequenced three full length genomes and 24 complete envelope sequences of DENV-2 from the years 2010, 2011 and 2013 collected from Punjab province of Pakistan
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