Abstract
BackgroundMother-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 FindingsWe 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.ConclusionThis study provides compelling evidence to support an important role of DC-SIGN in IU HIV-1 infection.
Highlights
In 2010, UNAIDS estimates that 390,000 children acquired HIV-1-infection worldwide mostly through mother-to-child transmission (MTCT) [1]
This study provides compelling evidence to support an important role of DC-SIGN in IU HIV-1 infection
We carried out an association study of DC-SIGN polymorphism in 197 infants born to antiretroviral therapy (ART)-naive HIV-1-infected mothers recruited in Harare, Zimbabwe [20]
Summary
In 2010, UNAIDS estimates that 390,000 children acquired HIV-1-infection worldwide mostly through mother-to-child transmission (MTCT) [1]. A better understanding of the mechanisms acting in MTCT of HIV-1 is crucial for the design of interventions other than ART for transmission prevention. IP transmission may occur through direct contact between infant mucosa and HIV-1 infected maternal blood and/ or cervico-vaginal secretions [2]. High maternal viral loads in serum and breast milk and low CD4 cell count as well as obstetric factors such as preterm delivery, vaginal delivery, and prolonged membrane rupture have been correlated with increased risk of MTCT of HIV-1 [2,3]. 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, known as CD209) is an HIV-1 receptor that enhances its transmission to T cells and is expressed on placental macrophages
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