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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/46943
Title: Joint ancestry and association test indicate two distinct pathogenic pathways involved in classical dengue fever and dengue shock syndrome
Authors: Marisa Oliveira
Worachart Lert-itthiporn
Bruno Cavadas
Verónica Fernandes
Ampaiwan Chuansumrit
Orlando Anunciação
Isabelle Casademont
Fanny Koeth
Marina Penova
Kanchana Tangnararatchakit
Chiea Chuen Khor
Richard Paul
Prida Malasit
Fumihiko Matsuda
Etienne Simon-Lorière
Prapat Suriyaphol
Luisa Pereira
Anavaj Sakuntabhai
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal
A-Star, Genome Institute of Singapore
Kyoto University Faculty of Medicine
National University of Singapore
Faculty of Medicine, Ramathibodi Hospital, Mahidol University
Thailand National Center for Genetic Engineering and Biotechnology
Faculty of Medicine, Siriraj Hospital, Mahidol University
CNRS Centre National de la Recherche Scientifique
Universidade do Porto
Institut Pasteur, Paris
Pasteur Kyoto International Joint Research Unit for Integrative Vaccinomics
Keywords: Medicine
Issue Date: 15-Feb-2018
Citation: PLoS Neglected Tropical Diseases. Vol.12, No.2 (2018)
Abstract: © 2018 Oliveira et al. 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.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85044376943&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/46943
ISSN: 19352735
19352727
Appears in Collections:Scopus 2018

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