Institut National de la Sante et de la Recherche Medicale (Inserm); Le Reseau International des Instituts Pasteur (RIIP); Institut Pasteur Paris; Mahidol University; Mahidol University; Mahidol University; CEA; UDICE-French Research Universities; Universite Paris Saclay; Mahidol University; Le Reseau International des Instituts Pasteur (RIIP); Institut Pasteur Paris; Mahidol University; National Science & Technology Development Agency - Thailand; National Center Genetic Engineering & Biotechnology (BIOTEC); Khon Kaen University; Ministry of Public Health - Thailand; Mahidol University; Mahidol University; Le Reseau International des Instituts Pasteur (RIIP); Institut Pasteur Paris
Type
Article
Source Title
NATURE GENETICS
Year
2005
Volume
37
Issue
5
Page
507-513
Open Access
Bronze, Green Published
Publisher
NATURE PUBLISHING GROUP
DOI
10.1038/ng1550
Format
PDF
Abstract
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(1,2). 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.
