Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0121696
Title: Clinical outcome and genetic differences within a monophyletic dengue virus type 2 population
Authors: Hapuarachchi H.C.
Chua R.C.R.
Shi Y.
Thein T.L.
Lee L.K.
Lee K.S.
Lye D.C. 
Ng L.C.
Leo Y.S. 
Keywords: nonstructural protein 2
nonstructural protein 2A
unclassified drug
3' untranslated region
epitope
virus RNA
3' untranslated region
5' untranslated region
amino acid substitution
Article
dengue
Dengue virus 2
disease course
disease severity
genetic difference
genome analysis
genotype
human
monophyly
nonhuman
nucleotide sequence
phylogeny
primary infection
secondary infection
Singapore
virus gene
virus genome
virus isolation
virus strain
adolescent
adult
aged
cohort analysis
conformation
dengue
Dengue virus
genetics
immunology
isolation and purification
middle aged
molecular genetics
phylogeny
treatment outcome
virology
young adult
Dengue virus
Dengue virus type 2
3' Untranslated Regions
Adolescent
Adult
Aged
Amino Acid Substitution
Cohort Studies
Dengue
Dengue Virus
Epitopes, B-Lymphocyte
Epitopes, T-Lymphocyte
Humans
Middle Aged
Molecular Sequence Data
Nucleic Acid Conformation
Phylogeny
RNA, Viral
Treatment Outcome
Young Adult
Issue Date: 2015
Citation: Hapuarachchi H.C., Chua R.C.R., Shi Y., Thein T.L., Lee L.K., Lee K.S., Lye D.C., Ng L.C., Leo Y.S. (2015). Clinical outcome and genetic differences within a monophyletic dengue virus type 2 population. PLoS ONE 10 (3) : e0121696. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0121696
Rights: Attribution 4.0 International
Abstract: The exact mechanisms of interplay between host and viral factors leading to severe dengue are yet to be fully understood. Even though previous studies have implicated specific genetic differences of Dengue virus (DENV) in clinical severity and virus attenuation, similar studies with large-scale, whole genome screening of monophyletic virus populations are limited. Therefore, in the present study, we compared 89 whole genomes of DENV-2 cosmopolitan clade III isolates obtained from patients diagnosed with dengue fever (DF, n = 58), dengue hemorrhagic fever (DHF, n = 30) and dengue shock syndrome (DSS, n = 1) in Singapore between July 2010 and January 2013, in order to determine the correlation of observed viral genetic differences with clinical outcomes. Our findings showed no significant difference between the number of primary and secondary infections that progressed to DHF and DSS (p>0.05) in our study cohort. Despite being highly homogenous, study isolates possessed 39 amino acid substitutions of which 10 substitutions were fixed in three main groups of virus isolates. None of those substitutions were specifically associated with DHF and DSS. Notably, two evolutionarily unique virus groups possessing C-P43T+NS1-S103T+NS2AV83I+NS3-R337K+NS3-I600T+ NS5-P136S and NS2A-T119N mutations were exclusively found in patients with DF, the benign form of DENV infections. Those mutants were significantly associated with mild disease outcome. These observations indicated that disease progression into DHF and DSS within our patient population was more likely to be due to host than virus factors. We hypothesize that selection for potentially less virulent groups of DENV-2 in our study cohort may be an evolutionary adaptation of viral strains to extend their survival in the human-mosquito transmission cycle. © 2015 Hapuarachchi et al.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/161737
ISSN: 19326203
DOI: 10.1371/journal.pone.0121696
Rights: Attribution 4.0 International
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