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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Naturally-occurring genetic variants in human DC-SIGN increase HIV-1 capture, cell-transfer and risk of mother-to-child transmission
PLoS ONE, Volume 7, No. 7, Article e40706, Year 2012
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Description
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. © 2012 Boily-Larouche et al.
Authors & Co-Authors
Boily-Larouche, Geneviève Ve
Canada, Montreal
Centre Hospitalier de L'universite de Montreal
Canada, Montreal
University of Montreal
Milev, Miroslav P.
Canada, Montreal
Institut Lady Davis de Recherches Médicales
Zijenah, Lynn Sodai
Zimbabwe, Harare
University of Zimbabwe
Labbé, Annie Claude
Canada, Montreal
University of Montreal
Canada, Montreal
Hôpital Maisonneuve-rosemont
Zannou, Djimon Marcel
Benin, Cotonou
University of Abomey-calavi
Humphrey, Jean H.
United States, Baltimore
Johns Hopkins Bloomberg School of Public Health
Ward, Brian James
Canada, Montreal
L'institut de Recherche du Centre Universitaire de Santé Mcgill
Poudrier, Johanne
Canada, Montreal
Centre Hospitalier de L'universite de Montreal
Canada, Montreal
University of Montreal
Mouland, Andrew J.
Canada, Montreal
Institut Lady Davis de Recherches Médicales
Cohen, Éric A.
Canada, Montreal
University of Montreal
Canada, Montreal
Institut de Recherches Cliniques de Montréal
Roger, Michel
Canada, Montreal
Centre Hospitalier de L'universite de Montreal
Canada, Montreal
University of Montreal
Statistics
Citations: 31
Authors: 11
Affiliations: 9
Identifiers
Doi:
10.1371/journal.pone.0040706
e-ISSN:
19326203
Research Areas
Genetics And Genomics
Infectious Diseases
Maternal And Child Health