title: Strategically examining the full-genome of dengue virus type 3 in clinical isolates reveals its mutation spectra.
abstract: BACKGROUND
  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. However, the extent of sequence variation among full genomic sequences of DENV within infected individuals remains largely unknown.
  
  
  RESULTS
  Instead 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 extent of 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.
  
  
  CONCLUSIONS
  This 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.
authors.affiliation: Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan 100, Republic of China. bmp3@cdc.gov
authors.forename: Day-Yu
authors.initials: DY
authors.lastname: Chao
authors.forename: Chwan-Chuen
authors.initials: CC
authors.lastname: King
authors.forename: Wei-Kung
authors.initials: WK
authors.lastname: Wang
authors.forename: Wei-June
authors.initials: WJ
authors.lastname: Chen
authors.forename: Hui-Lin
authors.initials: HL
authors.lastname: Wu
authors.forename: Gwong-Jen J
authors.initials: GJ
authors.lastname: Chang
mesh_terms: D000328:Adult; D001483:Base Sequence; D036022:Capsid Proteins / Q000235:genetics; D003715:Dengue / Q000453:epidemiology / Q000821:virology*; D003716:Dengue Virus / Q000235:genetics* / Q000302:isolation & purification; D004196:Disease Outbreaks; D016679:Genome, Viral; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D020365:RNA Helicases / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics; D013624:Taiwan / Q000453:epidemiology; D014759:Viral Envelope Proteins / Q000235:genetics; D017361:Viral Nonstructural Proteins / Q000235:genetics; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D036022:Capsid Proteins; D020365:RNA Helicases; D012697:Serine Endopeptidases; D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins; C084188:E protein, Dengue virus type 3; C060028:NS3 protein, flavivirus; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C096041:NS5 protein, flavivirus