Publication:
Joint ancestry and association test indicate two distinct pathogenic pathways involved in classical dengue fever and dengue shock syndrome

Issued Date

2018-02-15

Resource Type

Article

ISSN

19352735
19352727

DOI

10.1371/journal.pntd.0006202

Other identifier(s)

2-s2.0-85044376943

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

PLoS Neglected Tropical Diseases. Vol.12, No.2 (2018)

Suggested Citation

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 Joint ancestry and association test indicate two distinct pathogenic pathways involved in classical dengue fever and dengue shock syndrome. PLoS Neglected Tropical Diseases. Vol.12, No.2 (2018). doi:10.1371/journal.pntd.0006202 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/46943

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Title

Joint ancestry and association test indicate two distinct pathogenic pathways involved in classical dengue fever and dengue shock syndrome

Author(s)

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

Other Contributor(s)

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

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.

Keyword(s)

Medicine

Availability

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/46943

Collections

Scopus 2018