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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dendritic cells (DCs) are among the first cells encountered by human and simian immunodeficiency virus (HIV and SIV) following mucosal infection. Because these cells efficiently capture and transmit virus to T cells, they may play a major role in mediating HIV and SIV infection. Recently, a C-type lectin protein present on DCs, DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN), was shown to efficiently bind and present HIV and SIV to CD4(+), coreceptor-positive cells in trans. However, the significance of DC-SIGN for virus transmission and pathogenesis in vivo remains unclear. Because SIV infection of macaques may represent the best model to study the importance of DC-SIGN in HIV infection, we cloned and characterized pig-tailed macaque DC-SIGN and generated monoclonal antibodies (MAbs) against it. We demonstrate that, like human DC-SIGN, pig-tailed macaque DC-SIGN (ptDC-SIGN) is expressed on DCs and macrophages but not on monocytes, T cells, or B cells. Moderate levels of ptDC-SIGN expression were detected on the surface of DCs, and low-level expression was found on macrophages. Additionally, we show that ptDC-SIGN efficiently binds and transmits replication-competent SIVmne variants to CD4(+), coreceptor-positive cells. Moreover, transmission of virus between pig-tailed macaque DCs and CD4(+) T cells is largely ptDC-SIGN dependent. Interestingly, MAbs directed against ptDC-SIGN vary in the capacity to block transmission of different SIVmne variants. These data demonstrate that ptDC-SIGN plays a central role in transmitting virus from macaque DCs to T cells, and they suggest that SIVmne variants may differ in their interactions with ptDC-SIGN. Thus, SIVmne infection of pig-tailed macaques may provide an opportunity to investigate the significance of DC-SIGN in primate lentiviral infections.
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PMID:Capture and transfer of simian immunodeficiency virus by macaque dendritic cells is enhanced by DC-SIGN. 1241 25

Two CD209 family genes identified in humans, CD209 (DC-SIGN) and CD209L (DC-SIGNR/L-SIGN), encode C-type lectins that serve as adhesion receptors for ICAM-2 and ICAM-3 and participate in the transmission of human and simian immunodeficiency viruses (HIV and SIV, respectively) to target cells in vitro. Here we characterize the CD209 gene family in nonhuman primates and show that recent evolutionary alterations have occurred in this family across primate species. All of the primate species tested, specifically, Old World monkeys (OWM) and apes, have orthologues of human CD209. In contrast, CD209L is missing in OWM but present in apes. A third family member, that we have named CD209L2, was cloned from rhesus monkey cDNA and subsequently identified in OWM and apes but not in humans. Rhesus CD209L2 mRNA was prominently expressed in the liver and axillary lymph nodes, although preliminary data suggest that levels of expression may vary among individuals. Despite a high level of sequence similarity to both human and rhesus CD209, rhesus CD209L2 was substantially less effective at binding ICAM-3 and poorly transmitted HIV type 1 and SIV to target cells relative to CD209. Our data suggest that the CD209 gene family has undergone recent evolutionary processes involving duplications and deletions, the latter of which may be tolerated because of potentially redundant functional activities of the molecules encoded by these genes.
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PMID:Novel member of the CD209 (DC-SIGN) gene family in primates. 1247 27

Dendritic cells (DC) are instrumental in handling pathogens for processing and presentation to T cells, thus eliciting an appropriate immune response. C-type lectins expressed by DC function as pathogen-recognition receptors; yet their specificity for carbohydrate structures on pathogens is not fully understood. In this study, we analyzed the carbohydrate specificity of DC-specific ICAM-3-grabbing nonintegrin (SIGN)/CD209, the recently documented HIV-1 receptor on DC. Our studies show that DC-SIGN binds with high affinity to both synthetic mannose- and fucose-containing glycoconjugates. These carbohydrate structures are abundantly expressed by pathogens as demonstrated by the affinity of DC-SIGN for natural surface glycans of the human pathogens Mycobacterium tuberculosis, Helicobacter pylori, Leishmania mexicana, and Schistosoma mansoni. This analysis expands our knowledge on the carbohydrate and pathogen-specificity of DC-SIGN and identifies this lectin to be central in pathogen-DC interactions.
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PMID:Cutting edge: carbohydrate profiling identifies new pathogens that interact with dendritic cell-specific ICAM-3-grabbing nonintegrin on dendritic cells. 1257 25

Schistosoma mansoni soluble egg antigens (SEAs) are crucially involved in modulating the host immune response to infection by S. mansoni. We report that human dendritic cells bind SEAs through the C-type lectin dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN). Monoclonal antibodies against the carbohydrate antigens Lewisx (Lex) and GalNAcbeta1-4(Fucalpha1-3)GlcNAc (LDNF) inhibit binding of DC-SIGN to SEAs, suggesting that these glycan antigens may be critically involved in binding. In a solid-phase adhesion assay, DC-SIGN-Fc binds polyvalent neoglycoconjugates that contain the Lex antigen, whereas no binding was observed to Galbeta1-4GlcNAc, and binding to neoglycoconjugates containing only alpha-fucose or oligosaccharides with a terminal alpha1-2-linked fucose is low. These data indicate that binding of DC-SIGN to Lex antigen is fucose-dependent and that adjacent monosaccharides and/or the anomeric linkage of the fucose are important for binding activity. Previous studies have shown that DC-SIGN binds HIV gp120 that contains high-mannose-type N-glycans. Site-directed mutagenesis within the carbohydrate recognition domain (CRD) of DC-SIGN demonstrates that amino acids E324 and E347 are involved in binding to HIV gp120, Lex, and SEAs. By contrast, mutation of amino acid Val351 abrogates binding to SEAs and Lex but not HIV gp120. These data suggest that DC-SIGN recognizes these ligands through different (but overlapping) regions within its CRD. Our data imply that DC-SIGN not only is a pathogen receptor for HIV gp120 but may also function in pathogen recognition by interaction with the carbohydrate antigens Lex and possibly LDNF, which are found on important human pathogens, such as schistosomes and the bacterium Helicobacter pylori.
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PMID:The dendritic cell-specific C-type lectin DC-SIGN is a receptor for Schistosoma mansoni egg antigens and recognizes the glycan antigen Lewis x. 1262

C-type lectins are calcium-dependent carbohydrate-binding proteins with a wide range of biological functions, many of which are related to immunity. DC-SIGN (dendritic cell-specific ICAM-grabbing non-integrin, where ICAM is intercellular adhesion molecule) is a recently described mannose-specific C-type lectin expressed by dendritic cells. Dendritic cells are potent antigen-presenting cells capable of activating T-lymphocytes. DC-SIGN, which is expressed by dendritic cells, binds to ICAM-3 on T-lymphocytes, therefore playing an important role in the activation of T-lymphocytes. DC-SIGN can also bind HIV, and the virus may remain bound to DC-SIGN for protracted periods. DC-SIGN may deliver bound HIV to permissive cell types, mediating infection with high efficiency. A closely related C-type lectin, DC-SIGN-related molecule (DC-SIGNR) has also been described. DC-SIGNR is expressed by restricted subsets of endothelial cells, but has similar ICAM-3 and HIV-binding properties to DC-SIGN. This review describes the mapping of DC-SIGN and DC-SIGNR to chromosome 19p13.3 adjacent to the previously described C-type lectin, CD23 [the low-affinity receptor for immunoglobulin E (FcERII)]. The similar genomic organization of these three genes is discussed and consideration is given to the evolutionary duplications that may underlie this arrangement. Both DC-SIGN and DC-SIGNR possess a neck region, made up of multiple repeats, which supports the ligand-binding domain. Consideration is given to the biological reasons underlying the considerable polymorphism in the numbers of repeats in DC-SIGNR, but not DC-SIGN. The expression patterns of both DC-SIGN and DC-SIGNR are discussed in detail, with particular attention to the expression of both molecules in the placenta, which may have implications for the vertical transmission of HIV. Since dendritic cells may be important in determining the phenotype of many immune responses, via effects on T-lymphocytes, the differential expression of DC-SIGN by particular dendritic cell subsets may have important implications for the immunobiological functions of DC-SIGN. Similarly, the expression of DC-SIGNR by very restricted subsets of endothelial cells may give clues to the function of DC-SIGNR. Finally, the role of DC-SIGN in pathology, particularly in infective and neoplastic processes, is discussed, followed by speculation about likely future developments in this field.
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PMID:DC-SIGN (dendritic cell-specific ICAM-grabbing non-integrin) and DC-SIGN-related (DC-SIGNR): friend or foe? 1265 90

HIV pseudotypes bearing native hepatitis C virus (HCV) glycoproteins (strain H and Con1) are infectious for the human hepatoma cell lines Huh-7 and PLC/PR5. Infectivity depends on coexpression of both E1 and E2 glycoproteins, is pH-dependent, and can be neutralized by mAbs mapping to amino acids 412-447 within E2. Cell-surface expression of one or all of the candidate receptor molecules (CD81, low-density lipoprotein receptor, scavenger receptor class B type 1, and dendritic cell-specific intercellular adhesion molecule 3 grabbing nonintegrin) failed to confer permissivity to HIV-HCV pseudotype infection. However, HIV-HCV pseudotype infectivity was inhibited by a recombinant soluble form of CD81 and a mAb specific for CD81, suggesting that CD81 may be a component of a receptor complex.
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PMID:Hepatitis C virus glycoproteins mediate pH-dependent cell entry of pseudotyped retroviral particles. 1276 83

The dendritic cell (DC)-specific HIV-1 receptor DC-SIGN plays a key-role in the dissemination of HIV-1 by DCs. DC-SIGN captures HIV-1 at sites of entry, enabling its transport to lymphoid tissues, where DC-SIGN efficiently transmits low amounts of HIV-1 to T cells. The expression pattern of DC-SIGN in mucosal tissue, lymph nodes, placenta and blood suggests a function for DC-SIGN in both horizontal and vertical transmission of HIV-1. Moreover, the efficiency of DC-SIGN+ blood DC to transmit HIV-1 to T cells supports a role in HIV-1 transmission via blood. To date, DC-SIGN represents a novel class of HIV-1 receptor, because it does not allow viral infection but binds HIV-1 and enhances its infection of T cells in trans. Its unique function is further underscored by its restricted expression on DCs. Although DC-SIGN is a C-type lectin with an affinity for carbohydrates exemplified by its interaction with its immunological ligand ICAM-3, recent evidence demonstrates that glycosylation of gp120 is not necessary for its interaction with DC-SIGN. Moreover, mutational analysis demonstrates that the HIV-1 gp120 binding site in DC-SIGN is different from that of ICAM-3. Besides its role in DC-mediated adhesion processes, DC-SIGN also functions as an antigen receptor that captures and internalises antigens for presentation by DC. Strikingly, HIV-1 circumvents processing after binding DC-SIGN and remains infectious for several days after capture. A better understanding of the action of this novel HIV receptor in initial viral infection and subsequent transmission will provide a basis for the design of drugs that inhibit or alter interactions of DC-SIGN with gp120, interfering with HIV-1 dissemination and that may have a therapeutic value in both immunological diseases and/or HIV-1 infections.
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PMID:DC-SIGN: a novel HIV receptor on DCs that mediates HIV-1 transmission. 1279 42

Dendritic Cells (DC) are natural adjuvants able to elicit specific cellular interactions and priming of naive T cells at a mature stage of their differentiation. Recent genomic approaches helped defining DC or Langherans Cells (LC) in more molecular terms. DC-SIGN, the DC specific ICAM-3 grabbing non integrin is a C-type lectin, absent on LC but expressed on dermal, lymph node and tonsils DC. DC-SIGN is defined as an ICAM-3 receptor supporting DC mediated-T cell proliferation. Moreover, DC-SIGN plays an important role in binding and presentation of HIV virions, because DC-SIGN specifically binds the gp120 coat protein of HIV.DC-SIGN also plays a part in DC trafficking since it not only binds ICAM-3 but also ICAM-2 expressed by many endothelial cells, supporting tethering and rolling of DC on endothelium and chemokine induced-transmigration of DC across both resting and activated endothelium in vitro. ALCAM (Activated Leukocyte Cell Adhesion Molecule) is another cell surface protein expressed by DC upon differentiation from monocytes. ALCAM appears to be expressed on activated leukocytes and might be involved in inflammatory processes. ALCAM belongs to the IgG superfamily of proteins and mediate heterotypic (T cell antigen ligand CD6) or homotypic interactions. ALCAM is linked to the cytoskeleton and might play a role in DC migration. Measurements of cell/cell contacts at single molecular levels using optical traps is a useful tool to investigate intercellular interactions.
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PMID:Molecular characterization of dendritic cells operating at the interface of innate or acquired immunity. 1280 1

Langerhans cells (LCs) are suspected to be initial targets for HIV after sexual exposure (by becoming infected or by capturing virus). Here, productive R5 HIV infection of LC ex vivo and LC-mediated transmission of virus to CD4+ T cells were both found to depend on CCR5. By contrast, infection of monocyte-derived dendritic cells and transfer of infection from monocyte-derived dendritic cells to CD4+ T cells were mediated by CCR5-dependent as well as DC-specific ICAM-3-grabbing nonintegrin-dependent pathways. Furthermore, in 62 healthy individuals, R5 HIV infection levels in LCs ex vivo were associated with CCR5 genotype. Specifically, genotyping for ORF Delta 32 revealed that LCs isolated from ORF Delta 32/wt individuals were significantly less susceptible to HIV when compared with LCs isolated from ORFwt/wt individuals (P = 0.016). Strikingly, further genetic analyses of the A-2459G CCR5 promoter polymorphism in ORF Delta 32/wt heterozygous individuals revealed that LCs isolated from -2459A/G + ORF Delta 32/wt individuals were markedly less susceptible to HIV than were LCs from -2459A/A + ORF Delta 32/wt individuals (P = 0.012). Interestingly, these genetic susceptibility data in LCs parallel those of genetic susceptibility studies performed in cohorts of HIV-infected individuals. Thus, we suggest that CCR5-mediated infection of LCs, and not capture of virus by LCs, provides a biologic basis for understanding certain aspects of host genetic susceptibility to initial HIV infection.
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PMID:R5 HIV productively infects Langerhans cells, and infection levels are regulated by compound CCR5 polymorphisms. 1281 99

Dendritic cell (DC)-specific intercellular adhesion molecule 3 (ICAM-3) grabbing nonintegrin (DC-SIGN), a recently discovered type II transmembrane protein on DCs with a C-type lectin extracellular domain, is capable of binding ICAM-3 on resting T cells in the secondary lymphoid organs, providing the initial contact between these cells during the establishment of cell-mediated immunity. DC-SIGN also binds the HIV-1 envelope glycoprotein gp120 but does not function as a receptor for viral entry into DCs. Instead, DC-SIGN allows DCs in the peripheral mucosa to carry HIV-1 through the lymphatics in a "Trojan horse" fashion, where it is eventually delivered to the T cells. Also, the period of infectivity of HIV-1 is increased by several days as a result of DC-SIGN-gp120 binding, allowing for efficient trans-infection of T cells on DC arrival. The discovery of a cluster of related genes colocalized with DC-SIGN on chromosome 19p13.2-3, all displaying complex alternative splicing patterns, has led to a reexamination of the mechanisms underlying both the interactions between antigen-presenting cells (APCs) and T cells and the pathogenesis of HIV-1 infection.
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PMID:DC-SIGN points the way to a novel mechanism for HIV-1 transmission. 1460 1


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