Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

DC-SIGN and DC-SIGNR are two closely related membrane-associated C-type lectins that bind human immunodeficiency virus (HIV) envelope glycoprotein with high affinity. Binding of HIV to cells expressing DC-SIGN or DC-SIGNR can enhance the efficiency of infection of cells coexpressing the specific HIV receptors. DC-SIGN is expressed on some dendritic cells, while DC-SIGNR is localized to certain endothelial cell populations, including hepatic sinusoidal endothelial cells. We found that soluble versions of the hepatitis C virus (HCV) E2 glycoprotein and retrovirus pseudotypes expressing chimeric forms of both HCV E1 and E2 glycoproteins bound efficiently to DC-SIGN and DC-SIGNR expressed on cell lines and primary human endothelial cells but not to other C-type lectins tested. Soluble E2 bound to immature and mature human monocyte-derived dendritic cells (MDDCs). Binding of E2 to immature MDDCs was dependent on DC-SIGN interactions, while binding to mature MDDCs was partly independent of DC-SIGN, suggesting that other cell surface molecules may mediate HCV glycoprotein interactions. HCV interactions with DC-SIGN and DC-SIGNR may contribute to the establishment or persistence of infection both by the capture and delivery of virus to the liver and by modulating dendritic cell function.
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PMID:Hepatitis C virus glycoproteins interact with DC-SIGN and DC-SIGNR. 1263 66

The human immunodeficiency virus (HIV) is an enveloped virus whose surface glycoprotein gp120 binds CD4 on target cell membranes to initiate infection. About half of the carbohydrates on gp120 are terminally mannosylated, a pattern common to many pathogens. We have examined the ability of macrophage mannose receptor (MMR) on primary monocyte-derived macrophages to bind HIV and facilitate its transmission to T cells. We adapted the tyramide signal amplification system for fluorescence detection of HIV bound to macrophages. Our data show that approximately 60% of the initial association of HIV with macrophages that lack expression of DC-SIGN (a dendritic cell-specific ICAM-3 receptor/HIV-1-binding protein) is MMR mediated, as evidenced by inhibition with mannan, D-mannose, EDTA, and soluble mannose-binding lectin, but not by D-galactose. This inhibition is not seen in cells that lack MMR. Macrophages are able to mediate transmission of bound HIV to co-cultured T cells, and this transmission is blocked up to 80% by inhibitors of MMR binding. Unlike virus bound to DC-SIGN, macrophage-bound HIV has a slightly lower half-life compared to free virus, with no transmission in co-culture observed beyond 24 h after virus binding to macrophages. Results obtained with endocytosis inhibitors indicate that this decrease in viral longevity is due to rapid internalization of macrophage-bound HIV. Together, these results suggest a substantial role for MMR in the binding and transmission of HIV-1 by macrophages.
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PMID:Involvement of macrophage mannose receptor in the binding and transmission of HIV by macrophages. 1264 47

DC-SIGN, a lectin expressed on dendritic cell and macrophage subsets, binds to human immunodeficiency virus Env glycoproteins, allowing capture of viral particles. Captured virions either infect target cells or are efficiently transmitted to lymphocytes. Cellular mechanisms underlying the effects of DC-SIGN remain poorly understood. Here we have analyzed the effects of DC-SIGN on viral entry and on syncytium formation induced by Env glycoproteins. The lectin enhanced susceptibility to viral infection and dramatically increased virion internalization. Captured virions accumulated in the vesicular pathway, and their access to the cytosol was altered. Strikingly, the presence of DC-SIGN on target cells inhibited their ability to form syncytia with Env-expressing cells. However, increasing CD4 surface levels on target cells alleviated this inhibitory effect of DC-SIGN. Moreover, the potency of the viral fusion inhibitor T-20 was not affected in DC-SIGN-expressing cells. Altogether, our results indicate that DC-SIGN exerts subtle and complex effects during early steps of HIV type 1 replication. DC-SIGN facilitates capture and accumulation of viral particles in a vesicular compartment and inhibits viral fusion. Competition between CD4 and DC-SIGN for Env binding likely affects virus access to the cytosol and syncytium formation.
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PMID:Inhibition of human immunodeficiency virus type 1 Env-mediated fusion by DC-SIGN. 1269 33

Dendritic cells (DCs) can influence HIV-1 and SIV pathogenesis and protective mechanisms at several levels. First, HIV-1 productively infects select populations of DCs in culture, particularly immature DCs derived from blood monocytes and skin (Langerhans cells). However, there exist only a few instances in which HIV-1- or SIV-infected DCs have been identified in vivo in tissue sections. Second, different types of DCs reliably sequester and transmit infectious HIV-1 and SIV in culture, setting up a productive infection in T cells interacting with the DCs. This stimulation of infection in T cells may explain the observation that CD4+ T lymphocytes are the principal cell type observed to be infected with HIV-1 in lymphoid tissues in vivo. DCs express a C-type lectin, DC-SIGN/CD209, that functions to bind HIV-1 (and other infectious agents) and transmit virus to T cells. When transfected into the THP-1 cell line, the cytosolic domain of DC-SIGN is needed for HIV-1 sequestration and transmission. However, DCs lacking DC-SIGN (Langerhans cells) or expressing very low levels of DC-SIGN (rhesus macaque monocyte-derived DCs) may use additional molecules to bind and transmit immunodeficiency viruses to T cells. Third, DCs are efficient antigen-presenting cells for HIV-1 and SIV antigens. Infection with several recombinant viral vectors as well as attenuated virus is followed by antigen presentation to CD4+ and CD8+ T cells. An intriguing pathway that is well developed in DCs is the exogenous pathway for nonreplicating viral antigens to be presented on class I MHC products. This should allow DCs to stimulate CD8+ T cells after uptake of antibody-coated HIV-1 and dying infected T cells. It has been proposed that DCs, in addition to expanding effector helper and killer T cells, induce tolerance through T cell deletion and suppressor T cell formation, but this must be evaluated directly. Fourth, DCs are likely to be valuable in improving vaccine design. Increasing DC uptake of a vaccine, as well as increasing their numbers and maturation, should enhance efficacy. However, DCs can also capture antigens from other cells that are initially transduced with a DNA vaccine or a recombinant viral vector. The interaction of HIV-1 and SIV with DCs is therefore intricate but pertinent to understanding how these viruses disrupt immune function and elicit immune responses.
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PMID:The interaction of immunodeficiency viruses with dendritic cells. 1279 41

The modulation of plasma membrane proteins involved in the communication with the immune system is a general mechanism developed by viruses to escape the immune response. Most of the studied examples have focused on viral proteins that missort cellular proteins during their biosynthesis. However, an increasing number of examples show that the down-modulation can also be achieved after membrane delivery by targeting into the endocytic pathway. For both human immunodeficiency virus (HIV) and Kaposi sarcoma-associated herpesvirus (KSHV), the proteins required for this process are identified, Nef and K3/K5 respectively. The extensive studies in this field have shown that the mechanisms by which these proteins "parasite" the endocytic pathway are completely different. Nef directly interacts with components of the cellular machinery involved in the vesicular transport between the endocytic compartments, mainly the clathrin adaptor complexes (AP), inducing the misrouting of numerous cellular proteins, including CD4, MHC-I, LIGHT, DC-SIGN, CD28 and MHC-II to the endosomal degradation compartment or the trans Golgi-network. The K3 and K5 proteins from KSHV act by inducing the ubiquitylation of the target proteins, such as CMH-I and B7.2, triggering their internalization and subsequent degradation by the highly conserved Tsg101/vps23 ubiquitin-dependent endosomal pathway. While these findings show that the strategies used by viruses to target cellular proteins to the endocytic pathway are extremely diverse, additional investigations are needed for the complete understanding of the specific roles of Nef and K3/K5 in the physiopathology of HIV and KSHV infections, respectively. In addition, these viral factors represent valuable tools to study the pathway they are perturbing.
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PMID:[The HIV nef and the Kaposi-sarcoma-associated virus K3/K5 proteins: "parasites"of the endocytosis pathway]. 1283 98

Some dendritic cells (DC) express a cell-surface lectin called 'dendritic cell-specific intracellular adhesion molecule 3 (ICAM-3)-grabbing non-integrin' (DC-SIGN). DC-SIGN has been shown to mediate a type of infection called 'trans' infection, where DC bind human immunodeficiency virus (HIV) and efficiently transfer the virus to T cells. We investigated the possibility that mannose-binding lectin (MBL), a soluble lectin that functions as a recognition molecule in innate immunity and that binds to HIV, could block trans infection mediated by DC-SIGN. Binding studies with glycoprotein (gp)120/gp41-positive and -negative virus preparations suggested that DC-SIGN and MBL bind primarily to glycans on gp120/gp41, as opposed to glycans on host-cell-derived proteins, indicating a close overlap in the binding site of the two lectins and supporting the notion that MBL could prevent binding of HIV to DC-SIGN. Preincubation of X4, R5 or dual-tropic HIV strains with MBL prevented DC-SIGN-mediated trans infection of T cells. The mechanism of MBL blocking trans infection of T cells was at least partly caused by blocking of virus binding to DC-SIGN positive cells. This study shows that MBL prevents DC-SIGN-mediated trans infection of T cells in vitro and suggests that in infected persons, MBL may inhibit DC-SIGN-mediated uptake and spread of HIV.
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PMID:Inhibition of DC-SIGN-mediated trans infection of T cells by mannose-binding lectin. 1294 Nov 44

This study demonstrates that the human immunodeficiency virus (HIV) binding C-type lectin DC-SIGN is coexpressed with CD4 and CCR5 on dendritic cells/macrophages in human foreskin. It is hypothesised that DC-SIGN may contribute to the sexual transmission of HIV in the foreskin, by enabling infection of permissive cells in cis and/or in trans.
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PMID:Expression of DC-SIGN in human foreskin may facilitate sexual transmission of HIV. 1469 41

The process by which hepatitis C virus (HCV) enters cells and the reason for its hepatotropism remain obscure. Recently, the human immunodeficiency virus (HIV) binding lectins, DC-SIGN and DC-SIGNR, were shown to bind HCV. This article reports the expression of DC-SIGN and DC-SIGNR in HCV related liver disease and discusses whether these lectins, in particular DC-SIGNR, are responsible for HCV hepatotropism.
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PMID:HCV and HIV binding lectin, DC-SIGNR, is expressed at all stages of HCV induced liver disease. 1469 42

African green monkeys (AGMs) infected by simian immunodeficiency virus (SIV) SIVagm are resistant to AIDS. SIVagm-infected AGMs exhibit levels of viremia similar to those described during pathogenic human immunodeficiency virus type 1 (HIV-1) and SIVmac infections in humans and macaques, respectively, but contain lower viral loads in their lymph nodes. We addressed the potential role of dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN; CD209) in viral dissemination. In previous studies, it has been shown that human DC-SIGN and macaque DC-SIGN allow transmission of HIV and SIVmac to T cells. Here, we looked at the ability of DC-SIGN derived from AGM lymph nodes to interact with SIVagm. We show that DC-SIGN-expressing cells are present mainly in the medulla and often within the cortex and/or paracortex of AGM lymph nodes. We describe the isolation and characterization of at least three isoforms of dc-sign mRNA in lymph nodes of AGMs. The predicted amino acid sequence from the predominant mRNA isoform, DC-SIGNagm1, is 92 and 99% identical to the corresponding human and rhesus macaque DC-SIGN amino acid sequences, respectively. DC-SIGNagm1 is characterized by the lack of the fourth motif in the repeat domain. This deletion was also detected in the dc-sign gene derived from thirteen animals belonging to five other African monkey species and from four macaques (Macaca fascicularis and M. mulatta). Despite three- to seven-amino-acid modifications compared to DC-SIGNmac, DC-SIGNagm1 allows transmission of SIVagm to T cells. Furthermore, AGM monocyte-derived dendritic cells (MDDC) expressed at least 100,000 DC-SIGN molecules and were able to transmit SIVagm to T cells. At a low multiplicity of infection (10(-5) 50% tissue culture infective doses/cell), viral transmission by AGM MDDC was mainly DC-SIGN dependent. The present study reveals that DC-SIGN from a natural host species of SIV has the ability to act as an efficient attachment and transmission factor for SIVagm and suggests the absence of a direct link between this ability and viral load levels in lymph nodes.
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PMID:DC-SIGN from African green monkeys is expressed in lymph nodes and mediates infection in trans of simian immunodeficiency virus SIVagm. 1469 12

DC-SIGN, a specific C-type lectin expressed on dendritic cells, binds and transmits multiple strains of primate immunodeficiency viruses to susceptible cells. Here, we report that human DC-SIGN also captures feline immunodeficiency virus via high-affinity (1 nM), Ca(2+)-dependent, D-mannose-inhibited binding to the major envelope glycoprotein, gp95.
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PMID:Specific interaction of feline immunodeficiency virus surface glycoprotein with human DC-SIGN. 1496 64


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