Abstract
BackgroundPrevious studies presented the quasispecies spectrum of the envelope region of dengue virus type 3 (DENV-3) from either clinical specimens or field-caught mosquitoes. However, the extent of sequence variation among full genomic sequences of DENV within infected individuals remains largely unknown.ResultsInstead of arbitrarily choosing one genomic region in this study, the full genomic consensus sequences of six DENV-3 isolates were used to locate four genomic regions that had a higher potential of sequence heterogeneity at capsid-premembrane (C-prM), envelope (E), nonstructural protein 3 (NS3), and NS5. The extentof sequence heterogeneity revealed by clonal sequencing was genomic region-dependent, whereas the NS3 and NS5 had lower sequence heterogeneity than C-prM and E. Interestingly, the Phylogenetic Analysis by Maximum Likelihood program (PAML) analysis supported that the domain III of E region, the most heterogeneous region analyzed, was under the influence of positive selection.ConclusionThis study confirmed previous reports that the most heterogeneous region of the dengue viral genome resided at the envelope region, of which the domain III was under positive selection pressure. Further studies will need to address the influence of these mutations on the overall fitness in different hosts (i.e., mosquito and human) during dengue viral transmission.
Highlights
Previous studies presented the quasispecies spectrum of the envelope region of dengue virus type 3 (DENV-3) from either clinical specimens or field-caught mosquitoes
Like many RNA viruses, the genomic sequence of a single Dengue viruses (DENV) isolate exists in nature as a collection of highly similar but not identical variants known as quasispecies due to its high average mutation rate of 103 to 10-5substitution per nucleotide copied and per round of replication [5,6]
Heterogeneous regions identified at full genomic scale of DENV-3 To identify the potential heterogeneous regions of DENV3 in the whole-genomic scale, acute-phase plasma samples were obtained from six dengue patients, including three dengue fever (DF) and three dengue haemorrhagic fever (DHF) patients
Summary
Previous studies presented the quasispecies spectrum of the envelope region of dengue virus type 3 (DENV-3) from either clinical specimens or field-caught mosquitoes. Dengue viruses (DENV), which consisted of four antigenically distinct serotypes (DENV-1, 2, 3 and 4), are the most important arthropod-borne viruses affecting humans After infection, it may result in dengue fever (DF), dengue haemorrhagic fever (DHF), dengue shock syndrome (DSS) or death [1,2]. Previous studies using a clonal sequencing approach amplified viral RNA directly from DENV-3 infected patients' plasma and the extent of sequence heterogeneity in the envelope region with mean pairwise difference ranging from 0.21 to 1.67% have been observed [7]. The previous attempt to correlate the sequence heterogeneity of the capsid gene with NS protein 2B gene region of DENV-3 has observed very similar sequence heterogeneity with mean pairwise p-distance 0.12–1.2% [9], the extent of sequence variation among full genomic sequences of DENV within infected individuals remains largely unknown.
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