The molecular epidemiology of a dengue virus outbreak in Taiwan: population wide versus infrapopulation mutation analysis.
Dengue virus (DENV) causes approximately 390 million dengue infections worldwide every year. There were 22,777 reported DENV infections in Tainan, Taiwan in 2015. In this study, we sequenced the C-prM-E genes from 45 DENV 2015 strains, and phylogenetic analysis based on C-prM-E genes revealed that a...
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ftdoajarticles:oai:doaj.org/article:b6e83fe2dfe845829bb52acf8d79ecb0 2024-09-09T19:27:58+00:00 The molecular epidemiology of a dengue virus outbreak in Taiwan: population wide versus infrapopulation mutation analysis. You-Yuan Tsai Dayna Cheng Sheng-Wen Huang Su-Jhen Hung Ya-Fang Wang Yih-Jyh Lin Huey-Pin Tsai Justin Jang Hann Chu Jen-Ren Wang 2024-06-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0012268 https://doaj.org/article/b6e83fe2dfe845829bb52acf8d79ecb0 EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0012268 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0012268 https://doaj.org/article/b6e83fe2dfe845829bb52acf8d79ecb0 PLoS Neglected Tropical Diseases, Vol 18, Iss 6, p e0012268 (2024) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2024 ftdoajarticles https://doi.org/10.1371/journal.pntd.0012268 2024-08-05T17:49:03Z Dengue virus (DENV) causes approximately 390 million dengue infections worldwide every year. There were 22,777 reported DENV infections in Tainan, Taiwan in 2015. In this study, we sequenced the C-prM-E genes from 45 DENV 2015 strains, and phylogenetic analysis based on C-prM-E genes revealed that all strains were classified as DENV serotype 2 Cosmopolitan genotype. Sequence analysis comparing different DENV-2 genotypes and Cosmopolitan DENV-2 sequences prior to 2015 showed a clade replacement event in the DENV-2 Cosmopolitan genotype. Additionally, a major substitution C-A314G (K73R) was found in the capsid region which may have contributed to the clade replacement event. Reverse genetics virus rgC-A314G (K73R) showed slower replication in BHK-21 and C6/36 cells compared to wildtype virus, as well as a decrease in NS1 production in BHK-21-infected cells. After a series of passaging, the C-A314G (K73R) mutation reverted to wildtype and was thus considered to be unstable. Next generation sequencing (NGS) of three sera collected from a single DENV2-infected patient at 1-, 2-, and 5-days post-admission was employed to examine the genetic diversity over-time and mutations that may work in conjunction with C-A314G (K73R). Results showed that the number of haplotypes decreased with time in the DENV-infected patient. On the fifth day after admission, two new haplotypes emerged, and a single non-synonymous NS4A-L115I mutation was identified. Therefore, we have identified a persistent mutation C-A314G (K73R) in all of the DENV-2 isolates, and during the course of an infection, a single new non-synonymous mutation in the NS4A region appears in the virus population within a single host. The C-A314G (K73R) thus may have played a role in the DENV-2 2015 outbreak while the NS4A-L115I may be advantageous during DENV infection within the host. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 18 6 e0012268 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 You-Yuan Tsai Dayna Cheng Sheng-Wen Huang Su-Jhen Hung Ya-Fang Wang Yih-Jyh Lin Huey-Pin Tsai Justin Jang Hann Chu Jen-Ren Wang The molecular epidemiology of a dengue virus outbreak in Taiwan: population wide versus infrapopulation mutation analysis. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Dengue virus (DENV) causes approximately 390 million dengue infections worldwide every year. There were 22,777 reported DENV infections in Tainan, Taiwan in 2015. In this study, we sequenced the C-prM-E genes from 45 DENV 2015 strains, and phylogenetic analysis based on C-prM-E genes revealed that all strains were classified as DENV serotype 2 Cosmopolitan genotype. Sequence analysis comparing different DENV-2 genotypes and Cosmopolitan DENV-2 sequences prior to 2015 showed a clade replacement event in the DENV-2 Cosmopolitan genotype. Additionally, a major substitution C-A314G (K73R) was found in the capsid region which may have contributed to the clade replacement event. Reverse genetics virus rgC-A314G (K73R) showed slower replication in BHK-21 and C6/36 cells compared to wildtype virus, as well as a decrease in NS1 production in BHK-21-infected cells. After a series of passaging, the C-A314G (K73R) mutation reverted to wildtype and was thus considered to be unstable. Next generation sequencing (NGS) of three sera collected from a single DENV2-infected patient at 1-, 2-, and 5-days post-admission was employed to examine the genetic diversity over-time and mutations that may work in conjunction with C-A314G (K73R). Results showed that the number of haplotypes decreased with time in the DENV-infected patient. On the fifth day after admission, two new haplotypes emerged, and a single non-synonymous NS4A-L115I mutation was identified. Therefore, we have identified a persistent mutation C-A314G (K73R) in all of the DENV-2 isolates, and during the course of an infection, a single new non-synonymous mutation in the NS4A region appears in the virus population within a single host. The C-A314G (K73R) thus may have played a role in the DENV-2 2015 outbreak while the NS4A-L115I may be advantageous during DENV infection within the host. |
format |
Article in Journal/Newspaper |
author |
You-Yuan Tsai Dayna Cheng Sheng-Wen Huang Su-Jhen Hung Ya-Fang Wang Yih-Jyh Lin Huey-Pin Tsai Justin Jang Hann Chu Jen-Ren Wang |
author_facet |
You-Yuan Tsai Dayna Cheng Sheng-Wen Huang Su-Jhen Hung Ya-Fang Wang Yih-Jyh Lin Huey-Pin Tsai Justin Jang Hann Chu Jen-Ren Wang |
author_sort |
You-Yuan Tsai |
title |
The molecular epidemiology of a dengue virus outbreak in Taiwan: population wide versus infrapopulation mutation analysis. |
title_short |
The molecular epidemiology of a dengue virus outbreak in Taiwan: population wide versus infrapopulation mutation analysis. |
title_full |
The molecular epidemiology of a dengue virus outbreak in Taiwan: population wide versus infrapopulation mutation analysis. |
title_fullStr |
The molecular epidemiology of a dengue virus outbreak in Taiwan: population wide versus infrapopulation mutation analysis. |
title_full_unstemmed |
The molecular epidemiology of a dengue virus outbreak in Taiwan: population wide versus infrapopulation mutation analysis. |
title_sort |
molecular epidemiology of a dengue virus outbreak in taiwan: population wide versus infrapopulation mutation analysis. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2024 |
url |
https://doi.org/10.1371/journal.pntd.0012268 https://doaj.org/article/b6e83fe2dfe845829bb52acf8d79ecb0 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 18, Iss 6, p e0012268 (2024) |
op_relation |
https://doi.org/10.1371/journal.pntd.0012268 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0012268 https://doaj.org/article/b6e83fe2dfe845829bb52acf8d79ecb0 |
op_doi |
https://doi.org/10.1371/journal.pntd.0012268 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
18 |
container_issue |
6 |
container_start_page |
e0012268 |
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1809897284423385088 |