A variant in the CD209 promoter is associated with severity of dengue disease.
Anavaj Sakuntabhai
(1, 2)
,
Chairat Turbpaiboon
(1, 3)
,
Isabelle Casadémont
(1)
,
Ampaiwan Chuansumrit
(4)
,
Tassanee Lowhnoo
(1, 5, 6)
,
Anna Kajaste-Rudnitski
(7)
,
Sita Mint Kalayanarooj
(1, 8)
,
Kanchana Tangnararatchakit
(4)
,
Nattaya Tangthawornchaikul
(9)
,
Sirijit Vasanawathana
(10)
,
Wathanee Chaiyaratana
(6)
,
Pa-Thai Yenchitsomanus
(8, 9)
,
Prapat Suriyaphol
(8)
,
Panisadee Avirutnan
(8)
,
Kulkanya Chokephaibulkit
(11)
,
Fumihiko Matsuda
(5)
,
Sutee Yoksan
(12)
,
Yves Jacob
(13)
,
G Mark Lathrop
(5)
,
Prida Malasit
(8, 9)
,
Philippe Desprès
(7)
,
Cécile Julier
(1)
1
Génétique des Maladies Infectieuses et Autoimmunes
2 Department of Medicine, Faculty of Medicine
3 Department of Biochemistry, Faculty of Science
4 Department of Pediatrics, Faculty of Medicine
5 CNG - Centre National de Génotypage
6 Research Center, Faculty of Medicine
7 Interactions Moléculaires Flavivirus-Hôtes
8 Medical Molecular biology Unit, Faculty of Medicine
9 Medical Biotechnology Unit
10 Department of Pediatrics
11 Department of Pediatrics, Faculty of Medecine
12 Center for Vaccine Development
13 Génétique, Papillomavirus et Cancer Humain
2 Department of Medicine, Faculty of Medicine
3 Department of Biochemistry, Faculty of Science
4 Department of Pediatrics, Faculty of Medicine
5 CNG - Centre National de Génotypage
6 Research Center, Faculty of Medicine
7 Interactions Moléculaires Flavivirus-Hôtes
8 Medical Molecular biology Unit, Faculty of Medicine
9 Medical Biotechnology Unit
10 Department of Pediatrics
11 Department of Pediatrics, Faculty of Medecine
12 Center for Vaccine Development
13 Génétique, Papillomavirus et Cancer Humain
Anavaj Sakuntabhai
- Fonction : Auteur
- PersonId : 172917
- IdHAL : anavaj-sakuntabhai
- ORCID : 0000-0001-9099-6937
- IdRef : 182465500
Isabelle Casadémont
- Fonction : Auteur
- PersonId : 1259827
- IdHAL : isabelle-casademont
- ORCID : 0000-0002-3185-6405
Fumihiko Matsuda
- Fonction : Auteur
- PersonId : 758748
- ORCID : 0000-0003-4557-4553
Philippe Desprès
- Fonction : Auteur
- PersonId : 784493
- ORCID : 0000-0001-8926-4050
- IdRef : 033677379
Cécile Julier
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- Fonction : Auteur correspondant
- PersonId : 843211
Connectez-vous pour contacter l'auteur
Résumé
Dengue fever and dengue hemorrhagic fever are mosquito-borne viral diseases. Dendritic cell-specific ICAM-3 grabbing nonintegrin (DC-SIGN1, encoded by CD209), an attachment receptor of dengue virus, is essential for productive infection of dendritic cells. Here, we report strong association between a promoter variant of CD209, DCSIGN1-336, and risk of dengue fever compared with dengue hemorrhagic fever or population controls. The G allele of the variant DCSIGN1-336 was associated with strong protection against dengue fever in three independent cohorts from Thailand, with a carrier frequency of 4.7% in individuals with dengue fever compared with 22.4% in individuals with dengue hemorrhagic fever (odds ratio for risk of dengue hemorrhagic fever versus dengue fever: 5.84, P = 1.4 x 10(-7)) and 19.5% in controls (odds ratio for protection: 4.90, P = 2 x 10(-6)). This variant affects an Sp1-like binding site and transcriptional activity in vitro. These results indicate that CD209 has a crucial role in dengue pathogenesis, which discriminates between severe dengue fever and dengue hemorrhagic fever. This may have consequences for therapeutic and preventive strategies.