Rapid communication Polymorphisms in DC-SIGN and L-SIGN genes are associated with HIV-1 vertical transmission in a Northeastern Brazilian population Ronaldo Celerino da Silva a,b , Ludovica Segat c,⇑ , Valentina Zanin c , Luiz Claudio Arraes d , Sergio Crovella a a Department of Genetics, Federal University of Pernambuco (UFPE), Recife, PE, Brazil b Laboratory of Immunopathology Keizo Asami (LIKA), Federal University of Pernambuco (UFPE) Recife, PE, Brazil c Institute for Maternal and Child Health, IRCCS ‘‘Burlo Garofolo’’, Trieste, Italy d Instituto de Medicina Integral Prof. Fernando Figueira, Recife, PE, Brazil article info Article history: Received 13 April 2012 Accepted 30 July 2012 Available online 16 August 2012 abstract DC-SIGN and L-SIGN are receptors expressed on specialized macrophages in decidua, (Hofbauer and pla- cental capillary endothelial cells), known to interact with several pathogens, including HIV-1. To disclose the possible involvement of these molecules in the susceptibility to HIV vertical transmis- sion, we analyzed DC-SIGN and L-SIGN gene single nucleotide polymorphisms (SNPs) in 192 HIV-1 posi- tive children and 58 HIV-1 negative children all born to HIV-1 positive mothers, as well as 96 healthy uninfected children not exposed to HIV-1, all from Northeast Brazil. The frequency of three SNPs in the DC-SIGN promoter (139G > A, 201G > T and 336A > G) were sig- nificantly different when comparing HIV positive children with HIV-1 exposed uninfected children, indi- cating an association with susceptibility to HIV-1 vertical transmission. This genetic association suggests that DC-SIGN molecule may play a role in susceptibility to HIV-1 infection through vertical transmission. Ó 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved. 1. Introduction Mother to child HIV transmission (MTCT, or vertical transmis- sion), responsible for more than 90% of childhood HIV infections worldwide, can occur during pregnancy, delivery and breastfeed- ing. Over 2.5 million children under 15 years are infected by HIV- 1 and more than 250,000 children died only in 2009 [1]. At present, the rate of virus transmission from mother to child is around 2% when mother and child received antiretroviral therapy, while in the absence of any intervention transmission rates varies from 15% to 40% [2]. DC-SIGN (dendritic cell-specific ICAM-grabbing non-integrin) and L-SIGN (liver/lymph node-specific ICAM-grabbing non-inte- grin) are receptors expressed on specialized macrophages in decid- ua, Hofbauer cells (DC-SIGN) and placental capillary endothelial cells (L-SIGN), known to interact with a wide variety of pathogens, including HIV-1 [3]. These receptors are encoded by DC-SIGN and L-SIGN genes (also known as CD209 and CLEC4M respectively) both mapping on chromosome 19p13.2-3, sharing a similar intron–exon distribution and having 77% identity between their amino acid se- quences [3,4]. DC-SIGN and L-SIGN are organized into three distinct domains: an N-terminal cytoplasmic tail, a transmembrane do- main, and a C-terminal domain formed by a repeated region con- taining seven tandem repeats of 23 amino acids, and a carbohydrate recognition domain (CRD), involved in recognizing and binding to pathogens [3,5]. The interaction between DC-SIGN and L-SIGN and HIV-1 virus can increase the viral transfer to susceptible cells, indicating a probable involvement of these receptors in vertical transmission of the virus [4,6]. During pregnancy, the increase of DC-SIGN expression in placental tissues may reflect the augmented rates of HIV-1 vertical transmission, since the link between viral parti- cles and receptor allows the virus concentration in permissible cells surface, enabling viral entry into target cells through CD4 receptors and co-receptors. The virus bound to the receptor, can re- main viable for several days, leading to efficient transfer to T cells [4,7,8]. Moreover, HIV-1 is also able to infect Hofbauer cells that, when infected, may release infectious viral particles interacting with L-SIGN receptors expressed on placental capillaries endothelial cells and promote infection of T lymphocytes receptor-positive cir- culating in the blood. T cells and Hofbauer cells infected or with the virus adsorbed to the receptor, can move between the placenta and fetus [4,9,10]. 0198-8859/$36.00 - see front matter Ó 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.humimm.2012.07.338 ⇑ Corresponding author. Address: Institute for Maternal and Child Health IRCCS ‘‘Burlo Garofolo’’, Via dell’Istria 65/1, 34137 Trieste, Italy. E-mail address: segat@burlo.trieste.it (L. Segat). Human Immunology 73 (2012) 1159–1165 Contents lists available at SciVerse ScienceDirect www.ashi-hla.org journal homepage: www.elsevier.com/locate/humimm