Abstract | BACKGROUND: Mother-to-child transmission (MTCT) is the main cause of HIV-1 infection in children worldwide. Dendritic cell-specific ICAM-3 grabbing-nonintegrin ( DC-SIGN, also known as CD209) is an HIV-1 receptor that enhances its transmission to T cells and is expressed on placental macrophages. METHODS AND FINDINGS: We have investigated the association between DC-SIGN genetic variants and risk of MTCT of HIV-1 among Zimbabwean infants and characterized the impact of the associated mutations on DC-SIGN expression and interaction with HIV-1. DC-SIGN promoter (p-336C and p-201A) and exon 4 (198Q and 242V) variants were all significantly associated with increased risk of intrauterine (IU) HIV-1 infection. Promoter variants decreased DC-SIGN expression both in vitro and in placental CD163(+) macrophages (Hofbauer cells) of HIV-1 unexposed infants but not of HIV-1 exposed infants. The exon 4 protein-modifying mutations increased HIV-1 capture and transmission to T cells in vitro. CONCLUSION: This study provides compelling evidence to support an important role of DC-SIGN in IU HIV-1 infection.
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Authors | Geneviève Boily-Larouche, Miroslav P Milev, Lynn S Zijenah, Annie-Claude Labbé, Djimon M Zannou, Jean H Humphrey, Brian J Ward, Johanne Poudrier, Andrew J Mouland, Eric A Cohen, Michel Roger |
Journal | PloS one
(PLoS One)
Vol. 7
Issue 7
Pg. e40706
( 2012)
ISSN: 1932-6203 [Electronic] United States |
PMID | 22808239
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Cell Adhesion Molecules
- DC-specific ICAM-3 grabbing nonintegrin
- Lectins, C-Type
- Receptors, Cell Surface
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Topics |
- Base Sequence
- Cell Adhesion Molecules
(genetics)
- Female
- Genetic Variation
- HIV Infections
(genetics, transmission)
- HIV-1
(physiology)
- Haplotypes
(genetics)
- Humans
- Infant, Newborn
- Infectious Disease Transmission, Vertical
- Lectins, C-Type
(genetics)
- Macrophages
(metabolism)
- Molecular Sequence Data
- Placenta
(pathology)
- Polymorphism, Single Nucleotide
(genetics)
- Postpartum Period
- Pregnancy
- Promoter Regions, Genetic
(genetics)
- Receptors, Cell Surface
(genetics)
- T-Lymphocytes
(virology)
- Transcription, Genetic
- Zimbabwe
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