Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CIRE/mDC-SIGN is a C-type lectin we originally identified as a molecule differentially expressed by mouse dendritic cell (DC) populations. Immunostaining with a CIRE/mDC-SIGN-specific mAb revealed that CIRE/mDC-SIGN is indeed on the surface of some CD4+, CD4- 8- DCs and plasmacytoid pre-DCs, but not on CD8+ DCs. It has been proposed that CIRE/mDC-SIGN is the functional orthologue of human DC-SIGN (hDC-SIGN), a molecule that both enhances T cell responses and facilitates antigen uptake. We assessed if CIRE/mDC-SIGN and hDC-SIGN exhibit functional similarities. CIRE/mDC-SIGN is down-regulated upon activation, but unlike hDC-SIGN, incubation with IL-4 and IL-13 did not enhance CIRE/mDC-SIGN expression, indicating differences in gene regulation. Like hDC-SIGN, CIRE/mDC-SIGN bound mannosylated residues. However, we could detect no role for CIRE/mDC-SIGN in T cell-DC interactions and the protein did not bind to pathogens known to interact with hDC-SIGN, including Leishmania mexicana, cytomegalovirus, HIV and lentiviral particles bearing the Ebolavirus glycoprotein. The binding of CIRE/mDC-SIGN to hDC-SIGN ligands was not rescued when CIRE/mDC-SIGN was engineered to express the stalk region of hDC-SIGN. We conclude that there are significant differences in the fine specificity of the C-type lectin domains of hDC-SIGN and CIRE/mDC-SIGN and that these two molecules may not be functional orthologues.
 ...
PMID:Functional comparison of mouse CIRE/mouse DC-SIGN and human DC-SIGN. 1656 75

The clinical spectrum of leprosy is related to patients' immune responses. Non-responsiveness towards Mycobacterium leprae (ML) seems to correlate with a Th2 cytokine profile. The reason for such a polarized immune response remains unclear. The C-type lectin, DC-SIGN, expressed by subsets of dendritic cells (DCs) and macrophages, has previously been associated with Th2 responses. Here we show abundant DC-SIGN expression in lepromatous but not borderline tuberculoid leprosy, in both HIV-positive and HIV-negative patients. Moreover, we demonstrate that DC-SIGN can act as an entry receptor for ML, as it does for M. tuberculosis, through the cell wall component lipoarabinomannan. DC-SIGN is expressed on virtually all ML-containing cells, providing further evidence for its role as a receptor. DC-SIGN may therefore be induced on macrophages in lepromatous leprosy and may then contribute to mycobacterial entry into these cells.
 ...
PMID:DC-SIGN association with the Th2 environment of lepromatous lesions: cause or effect? 1658 55

Dendritic cells (DCs), the professional antigen presenting cells, are critical for host immunity by inducing specific immune responses against a broad variety of pathogens. Remarkably the human immunodeficiency virus-1 (HIV-1) subverts DC function leading to spread of the virus. At an early phase of HIV-1 transmission, DCs capture HIV-1 at mucosal surfaces and transmit the virus to T cells in secondary lymphoid tissues. Capture of the virus on DCs takes place via C-type lectins of which the dendritic cell-specific intercellular adhesion molecule-3 (ICAM-3) grabbing nonintegrin (DC-SIGN) is the best studied. DC-SIGN-captured HIV-1 particles accumulate in CD81(+) multivesicular bodies (MVBs) in DCs and are subsequently transmitted to CD4+ T cells resulting in infection of T cells. The viral cell-to-cell transmission takes place at the DC-T cell interface termed the infectious synapse. Recent studies demonstrate that direct infection of DCs contributes to the transmission to T cells at a later phase. Moreover, the infected DCs may function as cellular reservoirs for HIV-1. This review discusses the different processes that govern viral piracy of DCs by HIV-1, emphasizing the intracellular routing of the virus from capture on the cell surface to egress in the infectious synapse.
Curr HIV Res 2006 Apr
PMID:Viral piracy: HIV-1 targets dendritic cells for transmission. 1661 Oct 55

DC-SIGN (dendritic cell-specific ICAM-3 grabbing non-integrin) is a C-type lectin receptor of dendritic cells and is involved in the initial steps of numerous infectious diseases. Surface plasmon resonance has been used to study the affinity of a glycodendritic polymer with 32 mannoses, to DC-SIGN. This glycodendrimer binds to DC-SIGN surfaces in the submicromolar range. This binding depends on a clustered organization of DC-SIGN mimicking its natural organization as microdomain in the dendritic cells plasma membrane. Moreover, this compound inhibits DC-SIGN binding to the HIV glycoprotein gp120 with an IC50 in the micromolar range and therefore can be considered as a potential antiviral drug.
 ...
PMID:Mannose hyperbranched dendritic polymers interact with clustered organization of DC-SIGN and inhibit gp120 binding. 1661 22

The basic premise of whether transmission of HIV-1 through the oral mucosa actually occurs, and through what route, is a topic of intense interest. Our work has focused on HIV-1 receptors/co-receptors and alpha-defensin-1 in situ in human gingiva. Regardless of HIV-1 infection, the role that C-type lectin receptors might play in periodontal pathogenesis is of great interest. We have shown that the gingival lamina propria, when inflamed, becomes increasingly infiltrated with DC-SIGN+MR+ dermal dendritic cells (DDCs), while the inflamed epithelium shows a decrease in Langerin+ Langerhans cells (LCs). Moreover, DDCs and LCs contribute to the mature CD83+ DC pool in situ, and form immune conjugates with CD4+ T-cells in the lamina propria (Jotwani and Cutler, 2003). This raises the intriguing possibility that oral mucosal DCs may be involved in HIV-1 transfer to T-cells in situ. However, this possibility is tendered by the challenges faced by the virus in gaining access to oral mucosal immune cells, including their ability to survive the salivary defenses, cross the mucosal barrier, resist inactivation by alpha-defensins, and overcome the paucity of co-receptor CCR5 in (healthy) oral mucosa (i.e., required for productive infection [Jotwani et al., 2004]). To date, there is little evidence of direct infection by HIV-1 of oral mucosal DCs/T cells and other cells in situ. Abbreviations used in this paper: CP, chronic periodontitis; CCR5, chemokine receptor 5; CXCR4, C-X-C receptor 4; DCs, dendritic cells; DC-SIGN, DC-specific ICAM-3 grabbing non-integrin; DDC, dermal dendritic cells; LCs, Langerhans cells; LP, lamina propria; MR, mannose receptor.
 ...
PMID:Oral mucosal expression of HIV-1 receptors, co-receptors, and alpha-defensins: tableau of resistance or susceptibility to HIV infection? 1667 49

During natural HIV infection, an array of host receptors are thought to influence virus attachment and the kinetics of infection. In this study, to probe the interactions of HIV envelope (Env) with various receptors, we assessed the inhibitory properties of various anti-Env monoclonal antibodies (mAbs) in binding assays. To assist in detecting Env in attachment assays, we generated Fc fusions of full-length wild-type gp120 and several variable loop-deleted gp120s. Through investigation of the inhibition of Env binding to cell lines expressing CD4, CCR5, DC-SIGN, syndecans or combinations thereof, we found that the broadly neutralizing mAb, 2G12, directed to a unique carbohydrate epitope of gp120, inhibited Env-CCR5 binding, partially inhibited Env-DC-SIGN binding, but had no effect on Env-syndecan association. Furthermore, 2G12 inhibited Env attachment to primary monocyte-derived dendritic cells, that expressed CD4 and CCR5 primary HIV receptors, as well as DC-SIGN, and suggested that the dual activities of 2G12 could be valuable in vivo for inhibiting initial virus dissemination and propagation.
 ...
PMID:Inhibition of HIV Env binding to cellular receptors by monoclonal antibody 2G12 as probed by Fc-tagged gp120. 1681 62

Infection of T cells by HIV-1 can occur through binding of virus to dendritic cell (DC)-specific ICAM-3 grabbing nonintegrin (DC-SIGN) on dendritic cells and transfer of virus to CD4+ T cells. Here we show that a subset of B cells in the blood and tonsils of normal donors expressed DC-SIGN, and that this increased after stimulation in vitro with interleukin 4 and CD40 ligand, with enhanced expression of activation and co-stimulatory molecules CD23, CD58, CD80, and CD86, and CD22. The activated B cells captured and internalized X4 and R5 tropic strains of HIV-1, and mediated trans infection of T cells. Pretreatment of the B cells with anti-DC-SIGN monoclonal antibody blocked trans infection of T cells by both strains of HIV-1. These results indicate that DC-SIGN serves as a portal on B cells for HIV-1 infection of T cells in trans. Transmission of HIV-1 from B cells to T cells through this DC-SIGN pathway could be important in the pathogenesis of HIV-1 infection.
 ...
PMID:DC-SIGN on B lymphocytes is required for transmission of HIV-1 to T lymphocytes. 1683 1

Azurin, a member of a family of copper-containing proteins involved in electron transfer called cupredoxins, demonstrates structural features similar to the variable domains of the immunoglobulin superfamily members. An azurin-like protein called Laz with an additional N-terminal 39 amino acid peptide known as H.8 epitope is present on the surface of gonnococci and meningococci. We demonstrate that azurin, Laz and H.8-azurin can bind to the C-terminal cleavage product MSP1-19 of merozoite surface protein 1 (MSP1) of the malarial parasite Plasmodium falciparum and significantly reduce parasitemia. Azurin and Laz also bound strongly to HIV-1 gp120. Interestingly, azurin could not only bind to gp120 but also to the dendritic cell-specific adhesion receptor DC-SIGN, mimicking the functionality of the intercellular adhesion molecule ICAM-3 with which it also binds avidly. Furthermore, these three proteins significantly suppressed HIV-1 growth in peripheral blood mononuclear cells and such suppression appeared to be occurring at an entry stage in the infection process. The presence of both antimalarial and antiretroviral activity in azurin, H.8-azurin and Laz makes these proteins, or peptides derived from them, potential therapeutic agents in the treatment of malaria, HIV-1 infections or coinfections with both P. falciparum and HIV-1.
 ...
PMID:Azurin, Plasmodium falciparum malaria and HIV/AIDS: inhibition of parasitic and viral growth by Azurin. 1686 97

Platelets can engulf human immunodeficiency virus type 1 (HIV-1), and a significant amount of HIV-1 in the blood of infected individuals is associated with these cells. However, it is unclear how platelets capture HIV-1 and whether platelet-associated virus remains infectious. DC-SIGN and other lectins contribute to capture of HIV-1 by dendritic cells (DCs) and facilitate HIV-1 spread in DC/T-cell cocultures. Here, we show that platelets express both the C-type lectin-like receptor 2 (CLEC-2) and low levels of DC-SIGN. CLEC-2 bound to HIV-1, irrespective of the presence of the viral envelope protein, and facilitated HIV-1 capture by platelets. However, a substantial fraction of the HIV-1 binding activity of platelets was dependent on DC-SIGN. A combination of DC-SIGN and CLEC-2 inhibitors strongly reduced HIV-1 association with platelets, indicating that these lectins are required for efficient HIV-1 binding to platelets. Captured HIV-1 was maintained in an infectious state over several days, suggesting that HIV-1 can escape degradation by platelets and might use these cells to promote its spread. Our results identify CLEC-2 as a novel HIV-1 attachment factor and provide evidence that platelets capture and transfer infectious HIV-1 via DC-SIGN and CLEC-2, thereby possibly facilitating HIV-1 dissemination in infected patients.
 ...
PMID:DC-SIGN and CLEC-2 mediate human immunodeficiency virus type 1 capture by platelets. 1694 May 7

Most new cases of HIV-1 infection occur as the result of vaginal transmission. Identifying the phenotype and distribution of potential viral target cells in the vagina is important for understanding events in viral transmission and for developing effective prevention strategies. For example, compounds that prevent CD4 or CCR5 binding have been demonstrated recently to prevent vaginal transmission in rhesus macaques, but the expression and distribution of CCR5 has not been examined in the macaque vagina. The objective of this study was to examine the distribution and phenotype of cells and molecules in the vagina of rhesus macaques that may be involved in HIV transmission, including CCR5, CD3, CD4, CD8, CD1a, CD28, CD95, CD123 and HLA-DR. Normal juvenile and adult female rhesus macaques were examined by multicolor immunohistochemistry and flow cytometry. Although both CD4 and CCR5 were observed in the lamina propria, essentially no CD4 or CCR5 expression was detected within the squamous or keratinized layers of the vaginal epithelium. CCR5 expression was higher in the vaginal lamina propria of mature macaques compared to 1-3-year-old juveniles. The vast majority of CD4(+)CCR5(+) lymphocytes in the vagina had a central memory (CD95(+)CD28(+)) phenotype. Numerous CCR5-expressing dendritic cells (CD123(+)) or macrophages (CD68(+)) were observed in the lamina propria, but no CCR5, CD4 or DC-SIGN expression was detectable in the epithelium. Thus, the multiple layers of squamous epithelium normally covering the vaginal mucosa may provide an effective barrier against vaginal HIV-1 transmission. Microbicides that block CD4 or CCR5 expression may act within the deeper layers of the vaginal epithelium rather than on the epithelial surface.
 ...
PMID:Distribution of simian immunodeficiency virus target cells in vaginal tissues of normal rhesus macaques: implications for virus transmission. 1695 66


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>