Strategically examining the full-genome of dengue virus type 3 in clinical isolates reveals its mutation spectra.
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.
Chao
Day-Yu
DY
Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan 100, Republic of China. bmp3@cdc.gov
King
Chwan-Chuen
CC
Wang
Wei-Kung
WK
Chen
Wei-June
WJ
Wu
Hui-Lin
HL
Chang
Gwong-Jen J
GJ
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
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