HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Naturally-occurring genetic variants in human DC-SIGN increase HIV-1 capture, cell-transfer and risk of mother-to-child transmission.

AbstractBACKGROUND:
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.
AuthorsGeneviève 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
JournalPloS one (PLoS One) Vol. 7 Issue 7 Pg. e40706 ( 2012) ISSN: 1932-6203 [Electronic] United States
PMID22808239 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Cell Adhesion Molecules
  • DC-specific ICAM-3 grabbing nonintegrin
  • Lectins, C-Type
  • Receptors, Cell Surface
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

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: