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Evolution and heterogeneity of multiple serotypes of Dengue virus in Pakistan, 2006–2011
BACKGROUND: Even though dengue has been recognized as one of the major public health threats in Pakistan, the understanding of its molecular epidemiology is still limited. The genotypic diversity of Dengue virus (DENV) serotypes involved in dengue outbreaks since 2005 in Pakistan is not well studied...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3844417/ https://www.ncbi.nlm.nih.gov/pubmed/24007412 http://dx.doi.org/10.1186/1743-422X-10-275 |
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author | Koo, Carmen Nasir, Amna Hapuarachchi, Hapuarachchige Chanditha Lee, Kim-Sung Hasan, Zahra Ng, Lee-Ching Khan, Erum |
author_facet | Koo, Carmen Nasir, Amna Hapuarachchi, Hapuarachchige Chanditha Lee, Kim-Sung Hasan, Zahra Ng, Lee-Ching Khan, Erum |
author_sort | Koo, Carmen |
collection | PubMed |
description | BACKGROUND: Even though dengue has been recognized as one of the major public health threats in Pakistan, the understanding of its molecular epidemiology is still limited. The genotypic diversity of Dengue virus (DENV) serotypes involved in dengue outbreaks since 2005 in Pakistan is not well studied. Here, we investigated the origin, diversity, genetic relationships and geographic distribution of DENV to understand virus evolution during the recent expansion of dengue in Pakistan. METHODS: The study included 200 sera obtained from dengue-suspected patients from 2006 to 2011. DENV infection was confirmed in 94 (47%) sera by a polymerase chain reaction assay. These included 36 (38.3%) DENV-2, 57 DENV-3 (60.6%) and 1 DENV-4 (1.1%) cases. Sequences of 13 whole genomes (6 DENV-2, 6 DENV-3 and 1 DENV-4) and 49 envelope genes (26 DENV-2, 22 DENV-3 and 1 DENV-4) were analysed to determine the origin, phylogeny, diversity and selection pressure during virus evolution. RESULTS: DENV-2, DENV-3 and DENV-4 in Pakistan from 2006 to 2011 shared 98.5-99.6% nucleotide and 99.3-99.9% amino acid similarity with those circulated in the Indian subcontinent during the last decade. Nevertheless, Pakistan DENV-2 and DENV-3 strains formed distinct clades characterized by amino acid signatures of NS2A-I116T + NS5-K861R and NS3-K590R + NS5-S895L respectively. Each clade consisted of a heterogenous virus population that circulated in Southern (2006–2009) and Northern Pakistan (2011). CONCLUSIONS: DENV-2, DENV-3 and DENV-4 that circulated during 2006–2011 are likely to have first introduced via the southern route of Pakistan. Both DENV-2 and DENV-3 have undergone in-situ evolution to generate heterogenous populations, possibly driven by sustained local DENV transmission during 2006–2011 periods. While both DENV-2 and DENV-3 continued to circulate in Southern Pakistan until 2009, DENV-2 has spread in a Northern direction to establish in Punjab Province, which experienced a massive dengue outbreak in 2011. |
format | Online Article Text |
id | pubmed-3844417 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-38444172013-12-02 Evolution and heterogeneity of multiple serotypes of Dengue virus in Pakistan, 2006–2011 Koo, Carmen Nasir, Amna Hapuarachchi, Hapuarachchige Chanditha Lee, Kim-Sung Hasan, Zahra Ng, Lee-Ching Khan, Erum Virol J Research BACKGROUND: Even though dengue has been recognized as one of the major public health threats in Pakistan, the understanding of its molecular epidemiology is still limited. The genotypic diversity of Dengue virus (DENV) serotypes involved in dengue outbreaks since 2005 in Pakistan is not well studied. Here, we investigated the origin, diversity, genetic relationships and geographic distribution of DENV to understand virus evolution during the recent expansion of dengue in Pakistan. METHODS: The study included 200 sera obtained from dengue-suspected patients from 2006 to 2011. DENV infection was confirmed in 94 (47%) sera by a polymerase chain reaction assay. These included 36 (38.3%) DENV-2, 57 DENV-3 (60.6%) and 1 DENV-4 (1.1%) cases. Sequences of 13 whole genomes (6 DENV-2, 6 DENV-3 and 1 DENV-4) and 49 envelope genes (26 DENV-2, 22 DENV-3 and 1 DENV-4) were analysed to determine the origin, phylogeny, diversity and selection pressure during virus evolution. RESULTS: DENV-2, DENV-3 and DENV-4 in Pakistan from 2006 to 2011 shared 98.5-99.6% nucleotide and 99.3-99.9% amino acid similarity with those circulated in the Indian subcontinent during the last decade. Nevertheless, Pakistan DENV-2 and DENV-3 strains formed distinct clades characterized by amino acid signatures of NS2A-I116T + NS5-K861R and NS3-K590R + NS5-S895L respectively. Each clade consisted of a heterogenous virus population that circulated in Southern (2006–2009) and Northern Pakistan (2011). CONCLUSIONS: DENV-2, DENV-3 and DENV-4 that circulated during 2006–2011 are likely to have first introduced via the southern route of Pakistan. Both DENV-2 and DENV-3 have undergone in-situ evolution to generate heterogenous populations, possibly driven by sustained local DENV transmission during 2006–2011 periods. While both DENV-2 and DENV-3 continued to circulate in Southern Pakistan until 2009, DENV-2 has spread in a Northern direction to establish in Punjab Province, which experienced a massive dengue outbreak in 2011. BioMed Central 2013-09-04 /pmc/articles/PMC3844417/ /pubmed/24007412 http://dx.doi.org/10.1186/1743-422X-10-275 Text en Copyright © 2013 Koo et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Koo, Carmen Nasir, Amna Hapuarachchi, Hapuarachchige Chanditha Lee, Kim-Sung Hasan, Zahra Ng, Lee-Ching Khan, Erum Evolution and heterogeneity of multiple serotypes of Dengue virus in Pakistan, 2006–2011 |
title | Evolution and heterogeneity of multiple serotypes of Dengue virus in Pakistan, 2006–2011 |
title_full | Evolution and heterogeneity of multiple serotypes of Dengue virus in Pakistan, 2006–2011 |
title_fullStr | Evolution and heterogeneity of multiple serotypes of Dengue virus in Pakistan, 2006–2011 |
title_full_unstemmed | Evolution and heterogeneity of multiple serotypes of Dengue virus in Pakistan, 2006–2011 |
title_short | Evolution and heterogeneity of multiple serotypes of Dengue virus in Pakistan, 2006–2011 |
title_sort | evolution and heterogeneity of multiple serotypes of dengue virus in pakistan, 2006–2011 |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3844417/ https://www.ncbi.nlm.nih.gov/pubmed/24007412 http://dx.doi.org/10.1186/1743-422X-10-275 |
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