Association of DC-SIGN Promoter Polymorphism with Increased Risk for Parenteral, but Not Mucosal, Acquisition of Human Immunodeficiency Virus Type 1 Infection

Martin, Maureen P.; Lederman, Michael M.; Hutcheson, Holli; Goedert, James J.; Nelson, George W.; Kooyk, Yvette van; Detels, Roger; Buchbinder, Susan; Hoots, Keith; Vlahov, David; O’Brien, Stephen J.; Carrington, Mary

doi:10.1128/jvi.78.24.14053-14056.2004

Cited by 105 publications

(90 citation statements)

References 17 publications

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“…The participation of DC-SIGN in HIV infection has prompted studies to identify either DC-SIGN variants or polymorphisms that correlate with reduced or increased risk of HIV-1 infection. Heterozygosity of a DC-SIGN variant affecting the "neck" domain has been proposed to reduce the risk of HIV-1 infection (46), whereas a large study on the European-American population at risk for HIV infection has revealed that a single-nucleotide polymorphism in the DC-SIGN promoter associates with an increased risk for parenteral HIV-1 infection (19). This polymorphism affects a nucleotide included within the Ϫ468/Ϫ19 region and is located upstream of the PU.1-binding sites identified in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…In the case of HIV, DC-SIGN mediates virus binding and uptake by dendritic cells, where DC-SIGN-associated HIV remains infectious for prolonged periods of time and efficiently transfers HIV to CD4(ϩ) T cells in lymph nodes, where viral replication occurs (18). The critical function of DC-SIGN in HIV entry and spread is illustrated by the existence of DC-SIGN promoter polymorphisms associated with increased risk of parenteral infection by HIV-1 (19). Therefore, the identification of the regulatory sequences driving DC-SIGN basal and regulated expression might provide valuable information of potential diagnostic and therapeutic relevance.…”

mentioning

confidence: 99%

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PU.1 Regulates the Tissue-specific Expression of Dendritic Cell-specific Intercellular Adhesion Molecule (ICAM)-3-grabbing Nonintegrin

Domínguez-Soto¹,

Puig‐Kröger²,

Vega

et al. 2005

Journal of Biological Chemistry

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Dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) is a cell surface C-type lectin expressed on myeloid dendritic cells and certain tissue macrophages, which mediates antigen capture for processing and presentation and participates in intercellular interactions with naive T lymphocytes or endothelial cells. In their strategy to evade immunosurveillance, numerous pathogenic microorganisms, including human immunodeficiency virus and Mycobacterium, bind to DC-SIGN in order to gain access to dendritic cells. We present evidence that PU.1 dictates the basal and cell-specific activity of DC-SIGN gene-regulatory region through in vivo occupancy of two functional Ets elements, whose integrity is required for PU.1 responsiveness and for the cooperative actions of PU.1 and other transcription factors (Myb, RUNX) on the DC-SIGN gene proximal regulatory region. In addition, protein analysis and gene profiling experiments indicate that DC-SIGN and PU.1 are coordinately expressed upon classical and alternative macrophage activation and during dendritic cell maturation. Moreover, small interfering RNA-mediated reduction of PU.1 expression results in diminished DC-SIGN cellular levels. Altogether, these results indicate that PU.1 is involved in the myeloid-specific expression of DC-SIGN in myeloid cells, a contribution that can be framed within the role that PU.1 has on the acquisition of the antigen uptake molecular repertoire by dendritic cells and macrophages.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

PU.1 Regulates the Tissue-specific Expression of Dendritic Cell-specific Intercellular Adhesion Molecule (ICAM)-3-grabbing Nonintegrin

Domínguez-Soto¹,

Puig‐Kröger²,

Vega

et al. 2005

Journal of Biological Chemistry

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“…Results, in particular from the analysis of susceptibility to human immunodeficiency virus-1 or M. tuberculosis infection, remain under discussion. 11,[17][18][19][20][21][22][23] The usurpation of DC-SIGN and other family members by pathogens such as retroviruses, Ebola and Mycobacteria might have led to a pattern of distinctive patches or domains with the characteristic of positive selective pressure as a result of a genetic conflict. 6,13 Against this expectation, the evolutionary analysis of the family suggests both a pattern of apparent redundancy of CD209 genes (gene absence and gene loss) and of positive selection in specific lineages, in the context of a general pattern of gene conservation.…”

Section: 35mentioning

confidence: 99%

The evolutionary history of the CD209 (DC-SIGN) family in humans and non-human primates

et al. 2008

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The CD209 gene family that encodes C-type lectins in primates includes CD209 (DC-SIGN), CD209L (L-SIGN) and CD209L2. Understanding the evolution of these genes can help understand the duplication events generating this family, the process leading to the repeated neck region and identify protein domains under selective pressure. We compiled sequences from 14 primates representing 40 million years of evolution and from three non-primate mammal species. Phylogenetic analyses used Bayesian inference, and nucleotide substitutional patterns were assessed by codon-based maximum likelihood. Analyses suggest that CD209 genes emerged from a first duplication event in the common ancestor of anthropoids, yielding CD209L2 and an ancestral CD209 gene, which, in turn, duplicated in the common Old World primate ancestor, giving rise to CD209L and CD209. K A /K S values averaged over the entire tree were 0.43 (CD209), 0.52 (CD209L) and 0.35 (CD209L2), consistent with overall signatures of purifying selection. We also assessed the Toll-like receptor (TLR) gene family, which shares with CD209 genes a common profile of evolutionary constraint. The general feature of purifying selection of CD209 genes, despite an apparent redundancy (gene absence and gene loss), may reflect the need to faithfully recognize a multiplicity of pathogen motifs, commensals and a number of self-antigens.

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“…In this context, a recent study indicates that activation of DC by HPV L1-VLP is MyD88 dependent [34]. Polymorphisms in the DC-SIGN promoter were recently reported [35], but their effect on DC-SIGN binding and signaling has not yet been examined.…”

Section: Blocking the Interaction Of L1-vlp With Dc-sign Inhibits Vlpmentioning

confidence: 99%

Role of DC‐SIGN in the activation of dendritic cells by HPV‐16 L1 virus‐like particle vaccine

et al. 2006

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Dendritic cell-specific intercellular adhesion molecule-grabbing non-integrin (DC-SIGN), a specific C-type lectin expressed on DC, binds and transmits different pathogens to susceptible cells. In the present study, we examined the role of DC-SIGN in the capture of human papillomavirus (HPV) pseudovirions and activation of DC. We demonstrate that HPV virus-like particles (VLP) bind to DC-SIGN expressed on transfected Raji cells and that antibodies against DC-SIGN block this interaction. DC take up VLP, which activate expression of costimulatory markers and cytokines/ chemokines. Although our results indicate that DC-SIGN is not the major receptor for VLP in DC, this interaction contributes to the activation of DC surface antigens (HLA class I) and of various cytokines/chemokines, particularly TNF-a, IL-6, and RANTES. Induction of these markers in DC by VLP was significantly abrogated when binding to DC-SIGN was blocked by anti-DC-SIGN antibodies. These results suggest that DC-SIGN has a functional role in DC activation induced by HPV-16 L1-VLP, and thus highlight new aspects of DC interactions with HPV VLP. IntroductionThe C-type lectin dendritic cell-specific intercellular adhesion molecule-grabbing non-integrin (DC-SIGN; CD209) is a pathogen recognition receptor that interacts with mannose residues of glycoproteins in a calciumdependent manner via its C-terminal carbohydrate recognition domain [1,2]. DC-SIGN acts both as an adhesion molecule and pathogen recognition receptor, facilitating DC binding and internalization of several viruses, including HIV-1 [3].In addition to HIV, DC-SIGN was recently shown to bind a variety of microorganisms such as CMV [4], Ebola virus [5], Dengue virus [6], hepatitis C virus [7,8], simian immunodeficiency virus [9], Leishmania [10], Candida albicans [11], Mycobacterium [12][13][14] and Schistosoma [15]. Some pathogens subvert DC functions to escape immune surveillance [16]. DC-SIGN is abundantly expressed primarily on DC, including those derived from monocytes and those located beneath the genital surface [3].Human papillomavirus (HPV) virus-like particles (VLP) are a promising vaccine candidate for HPV and cervical cancer [17][18][19][20]. Recent clinical trials have shown that VLP afford excellent protection against persistent infection [20,21]. Because of the lack of a suitable cell culture system for in vitro propagation of HPV and the unavailability of virions, HPV VLP have been used as soluble surrogates for native virus particles. The routes of HPV-16 L1-VLP entry in DC and the nature of cellular receptors involved in capture have been studied but remain to be fully characterized. HPV VLP Here, we report that HPV-16 L1-VLP particles bind to DC-SIGN in transfected cell lines, and to a lesser extent in DC, and that this interaction participates in L1-VLPinduced activation of DC. Thus, DC-SIGN is likely involved in DC activation by HPV VLP. Results and discussion HPV L1-VLP bind to DC-SIGN in DC-SIGN-transfected cell linesTo study interactions between L1-VLP and DC-SIGN, we...

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Association of DC-SIGN Promoter Polymorphism with Increased Risk for Parenteral, but Not Mucosal, Acquisition of Human Immunodeficiency Virus Type 1 Infection

Cited by 105 publications

References 17 publications

PU.1 Regulates the Tissue-specific Expression of Dendritic Cell-specific Intercellular Adhesion Molecule (ICAM)-3-grabbing Nonintegrin

PU.1 Regulates the Tissue-specific Expression of Dendritic Cell-specific Intercellular Adhesion Molecule (ICAM)-3-grabbing Nonintegrin

The evolutionary history of the CD209 (DC-SIGN) family in humans and non-human primates

Role of DC‐SIGN in the activation of dendritic cells by HPV‐16 L1 virus‐like particle vaccine

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