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Joint ancestry and association test indicate two distinct pathogenic pathways involved in classical dengue fever and dengue shock syndrome
Ethnic diversity has been long considered as one of the factors explaining why the severe forms of dengue are more prevalent in Southeast Asia than anywhere else. Here we take advantage of the admixed profile of Southeast Asians to perform coupled association-admixture analyses in Thai cohorts. For...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5813895/ https://www.ncbi.nlm.nih.gov/pubmed/29447178 http://dx.doi.org/10.1371/journal.pntd.0006202 |
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author | Oliveira, Marisa Lert-itthiporn, Worachart Cavadas, Bruno Fernandes, Verónica Chuansumrit, Ampaiwan Anunciação, Orlando Casademont, Isabelle Koeth, Fanny Penova, Marina Tangnararatchakit, Kanchana Khor, Chiea Chuen Paul, Richard Malasit, Prida Matsuda, Fumihiko Simon-Lorière, Etienne Suriyaphol, Prapat Pereira, Luisa Sakuntabhai, Anavaj |
author_facet | Oliveira, Marisa Lert-itthiporn, Worachart Cavadas, Bruno Fernandes, Verónica Chuansumrit, Ampaiwan Anunciação, Orlando Casademont, Isabelle Koeth, Fanny Penova, Marina Tangnararatchakit, Kanchana Khor, Chiea Chuen Paul, Richard Malasit, Prida Matsuda, Fumihiko Simon-Lorière, Etienne Suriyaphol, Prapat Pereira, Luisa Sakuntabhai, Anavaj |
author_sort | Oliveira, Marisa |
collection | PubMed |
description | Ethnic diversity has been long considered as one of the factors explaining why the severe forms of dengue are more prevalent in Southeast Asia than anywhere else. Here we take advantage of the admixed profile of Southeast Asians to perform coupled association-admixture analyses in Thai cohorts. For dengue shock syndrome (DSS), the significant haplotypes are located in genes coding for phospholipase C members (PLCB4 added to previously reported PLCE1), related to inflammation of blood vessels. For dengue fever (DF), we found evidence of significant association with CHST10, AHRR, PPP2R5E and GRIP1 genes, which participate in the xenobiotic metabolism signaling pathway. We conducted functional analyses for PPP2R5E, revealing by immunofluorescence imaging that the coded protein co-localizes with both DENV1 and DENV2 NS5 proteins. Interestingly, only DENV2-NS5 migrated to the nucleus, and a deletion of the predicted top-linking motif in NS5 abolished the nuclear transfer. These observations support the existence of differences between serotypes in their cellular dynamics, which may contribute to differential infection outcome risk. The contribution of the identified genes to the genetic risk render Southeast and Northeast Asian populations more susceptible to both phenotypes, while African populations are best protected against DSS and intermediately protected against DF, and Europeans the best protected against DF but the most susceptible against DSS. |
format | Online Article Text |
id | pubmed-5813895 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-58138952018-03-02 Joint ancestry and association test indicate two distinct pathogenic pathways involved in classical dengue fever and dengue shock syndrome Oliveira, Marisa Lert-itthiporn, Worachart Cavadas, Bruno Fernandes, Verónica Chuansumrit, Ampaiwan Anunciação, Orlando Casademont, Isabelle Koeth, Fanny Penova, Marina Tangnararatchakit, Kanchana Khor, Chiea Chuen Paul, Richard Malasit, Prida Matsuda, Fumihiko Simon-Lorière, Etienne Suriyaphol, Prapat Pereira, Luisa Sakuntabhai, Anavaj PLoS Negl Trop Dis Research Article Ethnic diversity has been long considered as one of the factors explaining why the severe forms of dengue are more prevalent in Southeast Asia than anywhere else. Here we take advantage of the admixed profile of Southeast Asians to perform coupled association-admixture analyses in Thai cohorts. For dengue shock syndrome (DSS), the significant haplotypes are located in genes coding for phospholipase C members (PLCB4 added to previously reported PLCE1), related to inflammation of blood vessels. For dengue fever (DF), we found evidence of significant association with CHST10, AHRR, PPP2R5E and GRIP1 genes, which participate in the xenobiotic metabolism signaling pathway. We conducted functional analyses for PPP2R5E, revealing by immunofluorescence imaging that the coded protein co-localizes with both DENV1 and DENV2 NS5 proteins. Interestingly, only DENV2-NS5 migrated to the nucleus, and a deletion of the predicted top-linking motif in NS5 abolished the nuclear transfer. These observations support the existence of differences between serotypes in their cellular dynamics, which may contribute to differential infection outcome risk. The contribution of the identified genes to the genetic risk render Southeast and Northeast Asian populations more susceptible to both phenotypes, while African populations are best protected against DSS and intermediately protected against DF, and Europeans the best protected against DF but the most susceptible against DSS. Public Library of Science 2018-02-15 /pmc/articles/PMC5813895/ /pubmed/29447178 http://dx.doi.org/10.1371/journal.pntd.0006202 Text en © 2018 Oliveira et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Oliveira, Marisa Lert-itthiporn, Worachart Cavadas, Bruno Fernandes, Verónica Chuansumrit, Ampaiwan Anunciação, Orlando Casademont, Isabelle Koeth, Fanny Penova, Marina Tangnararatchakit, Kanchana Khor, Chiea Chuen Paul, Richard Malasit, Prida Matsuda, Fumihiko Simon-Lorière, Etienne Suriyaphol, Prapat Pereira, Luisa Sakuntabhai, Anavaj Joint ancestry and association test indicate two distinct pathogenic pathways involved in classical dengue fever and dengue shock syndrome |
title | Joint ancestry and association test indicate two distinct pathogenic pathways involved in classical dengue fever and dengue shock syndrome |
title_full | Joint ancestry and association test indicate two distinct pathogenic pathways involved in classical dengue fever and dengue shock syndrome |
title_fullStr | Joint ancestry and association test indicate two distinct pathogenic pathways involved in classical dengue fever and dengue shock syndrome |
title_full_unstemmed | Joint ancestry and association test indicate two distinct pathogenic pathways involved in classical dengue fever and dengue shock syndrome |
title_short | Joint ancestry and association test indicate two distinct pathogenic pathways involved in classical dengue fever and dengue shock syndrome |
title_sort | joint ancestry and association test indicate two distinct pathogenic pathways involved in classical dengue fever and dengue shock syndrome |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5813895/ https://www.ncbi.nlm.nih.gov/pubmed/29447178 http://dx.doi.org/10.1371/journal.pntd.0006202 |
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