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Naturally-Occurring Genetic Variants in Human DC-SIGN Increase HIV-1 Capture, Cell-Transfer and Risk of Mother-To-Child Transmission
Published: Tuesday, July 10, 2012
Author: Geneviève Boily-Larouche et al.

by 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, Éric A. Cohen, Michel Roger


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.


This study provides compelling evidence to support an important role of DC-SIGN in IU HIV-1 infection.