Clinical outcome and genetic differences within a monophyletic Dengue virus type 2 population.
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, who...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4374945?pdf=render |
| _version_ | 1818265535535644672 |
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| author | Hapuarachchige Chanditha Hapuarachchi Rachel Choon Rong Chua Yuan Shi Tun Lin Thein Linda Kay Lee Kim Sung Lee David Chien Lye Lee Ching Ng Yee Sin Leo |
| author_facet | Hapuarachchige Chanditha Hapuarachchi Rachel Choon Rong Chua Yuan Shi Tun Lin Thein Linda Kay Lee Kim Sung Lee David Chien Lye Lee Ching Ng Yee Sin Leo |
| author_sort | Hapuarachchige Chanditha Hapuarachchi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T19:52:21Z |
| format | Article |
| id | doaj.art-4efcd887fc7042d5ad66ed7b968c7446 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T19:52:21Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-4efcd887fc7042d5ad66ed7b968c74462022-12-22T00:13:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01103e012169610.1371/journal.pone.0121696Clinical outcome and genetic differences within a monophyletic Dengue virus type 2 population.Hapuarachchige Chanditha HapuarachchiRachel Choon Rong ChuaYuan ShiTun Lin TheinLinda Kay LeeKim Sung LeeDavid Chien LyeLee Ching NgYee Sin LeoThe 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.http://europepmc.org/articles/PMC4374945?pdf=render |
| spellingShingle | Hapuarachchige Chanditha Hapuarachchi Rachel Choon Rong Chua Yuan Shi Tun Lin Thein Linda Kay Lee Kim Sung Lee David Chien Lye Lee Ching Ng Yee Sin Leo Clinical outcome and genetic differences within a monophyletic Dengue virus type 2 population. PLoS ONE |
| title | Clinical outcome and genetic differences within a monophyletic Dengue virus type 2 population. |
| title_full | Clinical outcome and genetic differences within a monophyletic Dengue virus type 2 population. |
| title_fullStr | Clinical outcome and genetic differences within a monophyletic Dengue virus type 2 population. |
| title_full_unstemmed | Clinical outcome and genetic differences within a monophyletic Dengue virus type 2 population. |
| title_short | Clinical outcome and genetic differences within a monophyletic Dengue virus type 2 population. |
| title_sort | clinical outcome and genetic differences within a monophyletic dengue virus type 2 population |
| url | http://europepmc.org/articles/PMC4374945?pdf=render |
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