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Basic Characteristics of Mutations
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Mutation Site
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P43T |
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Mutation Site Sentence
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Notably, two evolutionarily unique virus groups possessing C-P43T+NS1-S103T+NS2A-V83I+NS3-R337K+ NS3-I600T+ NS5-P136S and NS2A-T119N mutations were exclusively found in patients with DF, the benign form of DENV infections. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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C |
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Standardized Encoding Gene
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Capsid
|
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Genotype/Subtype
|
DENV-2 Genotype III |
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Viral Reference
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NC001474
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Functional Impact and Mechanisms
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Disease
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Dengue
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Immune
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- |
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Target Gene
|
-
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Clinical and Epidemiological Correlations
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Clinical Information
|
Y |
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Treatment
|
- |
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Location
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Singapore |
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Literature Information
|
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PMID
|
25811657
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Title
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Clinical outcome and genetic differences within a monophyletic Dengue virus type 2 population
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Author
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Hapuarachchi HC,Chua RC,Shi Y,Thein TL,Lee LK,Lee KS,Lye DC,Ng LC,Leo YS
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Journal
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PloS one
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Journal Info
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2015 Mar 26;10(3):e0121696
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Abstract
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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+NS2A-V83I+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.
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Sequence Data
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KM279513-KM279610
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