Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immature dendritic cells (iDCs) express the CC chemokine receptor (CCR)5, which promotes chemotaxis toward the CC chemokines regulated on activation, normal T cell expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta. By contrast, mature DCs downregulate CCR5 but upregulate CXC chemokine receptor (CXCR)4, and as a result exhibit enhanced chemotaxis toward stromal cell-derived factor (SDF)-1alpha. CCR5 and CXCR4 also function as coreceptors for macrophage-tropic (M-tropic) and T cell-tropic (T-tropic) human immunodeficiency virus (HIV)-1, respectively. Here, we demonstrate chemotaxis of iDCs toward M-tropic (R5) but not T-tropic (X4) HIV-1. Furthermore, preexposure to M-tropic HIV-1 or its recombinant envelope protein prevents migration toward CCR5 ligands. The migration of iDCs toward M-tropic HIV-1 may enhance formation of DC-T cell syncytia, thus promoting viral production and destruction of both DC and T helper lymphocytes. Therefore, disturbance of DC chemotaxis by HIV-1 is likely to contribute to immunosuppression in primary infection and AIDS. In addition, migration of iDCs toward HIV-1 may aid the capture of R5 HIV-1 virions by the abundant DC cell surface protein DC-specific intercellular adhesion molecule (ICAM)3-grabbing nonintegrin (DC-SIGN). HIV-1 bound to DC cell-specific DC-SIGN retains the ability to infect replication-permissive T cells in trans for several days. Consequently, recruitment of DC by HIV-1 could combine with the ability of DC-SIGN to capture and transmit the virus to T cells, and so facilitate dissemination of virus within an infected individual.
 ...
PMID:Macrophage-tropic HIV induces and exploits dendritic cell chemotaxis. 1095 29

The discovery of dendritic cell (DC)-specific intercellular adhesion molecule (ICAM)-3-grabbing nonintegrin (DC-SIGN) as a DC-specific ICAM-3 binding receptor that enhances HIV-1 infection of T cells in trans has indicated a potentially important role for adhesion molecules in AIDS pathogenesis. A related molecule called DC-SIGNR exhibits 77% amino acid sequence identity with DC-SIGN. The DC-SIGN and DC-SIGNR genes map within a 30-kb region on chromosome 19p13.2-3. Their strong homology and close physical location indicate a recent duplication of the original gene. Messenger RNA and protein expression patterns demonstrate that the DC-SIGN-related molecule is highly expressed on liver sinusoidal cells and in the lymph node but not on DCs, in contrast to DC-SIGN. Therefore, we suggest that a more appropriate name for the DC-SIGN-related molecule is L-SIGN, liver/lymph node-specific ICAM-3-grabbing nonintegrin. We show that in the liver, L-SIGN is expressed by sinusoidal endothelial cells. Functional studies indicate that L-SIGN behaves similarly to DC-SIGN in that it has a high affinity for ICAM-3, captures HIV-1 through gp120 binding, and enhances HIV-1 infection of T cells in trans. We propose that L-SIGN may play an important role in the interaction between liver sinusoidal endothelium and trafficking lymphocytes, as well as function in the pathogenesis of HIV-1.
 ...
PMID:A dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN)-related protein is highly expressed on human liver sinusoidal endothelial cells and promotes HIV-1 infection. 1125 34

The extent to which simian immunodeficiency virus (SIV) replication in lung tissues contributes to the pool of viruses replicating during acute infection is incompletely understood. To address this issue, in situ hybridization was used to examine SIV replication in multiple lobes of lung from rhesus macaques infected with pathogenic SIV. Despite widespread viral replication in lymphoid and intestinal tissues, the lungs during acute infection harbored rare productively infected cells. Simultaneous immunohistochemical staining for the monocytic marker, CD68, revealed that SIV RNA(+) cells in lung tissues during acute infection were CD68(-), whereas during AIDS they were predominantly CD68(+) and localized in large foci in caudal lobes. SIV RNA(+) cells in spleen remained CD68(-) throughout disease. Since CD68 is also expressed by subpopulations of dendritic cells (DC), we also examined pulmonary CD68(+) cells for expression of additional DC markers. DC-LAMP mRNA was abundant in lung tissues and expressed predominantly by CD68(-) cells, whereas DC-SIGN mRNA was expressed in only very rare cells, indicating that SIV RNA(+) cells late in disease were most likely macrophages. These studies of SIV/host interactions demonstrate that macaque lung tissues are minimally infected during acute infection, exhibit changes in predominant target cells for infection, and express very little DC-SIGN.
 ...
PMID:Restricted SIV replication in rhesus macaque lung tissues during the acute phase of infection. 1221 25

We report here the gene for DC-SIGN from Chinese rhesus macaques. DC-SIGN is a C-type lectin expressed by dendritic cells (DCs). It is involved in the interaction of DCs with T cells, and in transmission to T cells of HIV-1 and SIV. Alternative splicing in human DC-SIGN yields A and B isoforms of the protein. The overall organization of the rhesus macaque gene is similar to that of the human gene. Translation of B isoforms cannot occur because of a point substitution. The coding sequence shows that we have cloned a fourth allele for rhesus macaque DC-SIGN. This allele shows high homology to the other rhesus macaque alleles. However, at the protein level, the homology is highest with the pigtail macaque protein. This suggests a convergent evolution of DC-SIGN in macaques living in China. The importance of DC-SIGN variability in the immune response remains to be investigated.
AIDS Res Hum Retroviruses 2002 Sep 01
PMID:Gene for chinese rhesus macaque DC-SIGN predicts the existence of A but not B isoforms of the protein. 1223 Sep 40

DC-SIGN (dendritic cell-specific ICAM-3 grabbing nonintegrin), an external C-type lectin expressed on dendritic cells (DCs), has been proposed to play a pivotal role in trafficking HIV/SIV from mucosal surfaces to lymphoid tissues. Although the location of DC-SIGN expression has been established in a limited number of human tissues, its distribution in the rhesus macaque has not yet been determined. This study characterized the distribution and immunophenotype of DC-SIGN-expressing cells in SIV-infected and uninfected macaque tissues by immunohistochemistry (IHC) and confocal microscopy. IHC, using monoclonal and polyclonal antibodies against DC-SIGN, was performed on a variety of tissues. To further define the immunophenotype of DC-SIGN(+) cells, double-labeling with antibodies to CD68, fascin, and HLA-DR was done. In both infected and uninfected macaques, DC-SIGN(+) cells were located within the submucosa and lamina propria of tongue, vagina, rectum, and tonsil; however, no positive cells were present within the epithelium of any tissue. Antibodies to DC-SIGN also labeled Kupffer cells within the liver and scattered perivascular cells in the brain. Within lymph nodes, numerous positive cells were present within sinusoids in addition to cells consistent with interdigitating reticular cells in the paracortex and scattered follicular dendritic cells within germinal centers. In spleen of uninfected macaques, there was a similar distribution of DC-SIGN(+) cells with sinusoidal, marginal zone, and interdigitating dendritic cells staining; however, there was a marked paucity of staining in the spleens of SIV-infected macaques. DC-SIGN(+) cells were consistently CD68(+), but fascin(-) and HLA-DR(-). The absence of intraepithelial DC-SIGN-positive cells in mucosal tissues suggests that DC-SIGN does not play a significant role in transmucosal passage of HIV/SIV.
AIDS Res Hum Retroviruses 2002 Sep 20
PMID:Distribution and immunophenotype of DC-SIGN-expressing cells in SIV-infected and uninfected macaques. 1239 54

Dendritic cells (DCs) are potent antigen-presenting cells that likely play multiple roles in human immunodeficiency virus type 1 (HIV-1) pathogenesis. We used the simian immunodeficiency virus (SIV)/macaque model to study the effects of infection on homeostatic chemokine expression and DC localization directly in secondary lymphoid tissues. SIV infection altered the expression of chemokines (CCL19/MIP-3beta, CCL21/ 6Ckine, and CCL20/MIP-3alpha) and of chemokine receptors (CCR7 and CCR6) that drive DC trafficking. CCL19/MIP-3beta, CCL20/MIP-3alpha, CCR6, and CCR7 expression increased in lymph nodes during the early systemic burst of viral replication (acute infection), whereas CCL21/6Ckine expression progressively decreased throughout disease to AIDS. Parallel with the SIV-induced perturbations in chemokine expression were changes in the expression of the DC-associated markers, DC-SIGN, DC-LAMP, and DECTIN-1. During AIDS, DC-LAMP mRNA expression levels were significantly reduced in lymph nodes and spleen, and DC-SIGN levels were significantly reduced in spleen. These findings suggest that the disruption of homeostatic chemokine expression is responsible, in part, for alterations in the networks of antigen-presenting cells in lymphoid tissues, ultimately contributing to systemic immunodeficiency.
 ...
PMID:Simian immunodeficiency virus dramatically alters expression of homeostatic chemokines and dendritic cell markers during infection in vivo. 1240 87

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.
 ...
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 dendritic Cell-specific adhesion receptor and a type II transmembrane mannose-binding C-type lectin, is very important in the function of DC, both in mediating naive T cell interactions through ICAM-3 and as a rolling receptor that mediates the DC-specific ICAM-2-dependent migration processes. It can be used by viral and bacterial pathogens including Human Immunodeficiency Virus (HIV), HCV, Ebola Virus, CMV and Mycobacterium tuberculosis to facilitate infection. Both DC-SIGN and DC-SIGNR can act either in cis, by concentrating virus on target cells, or in trans, by transmission of bound virus to a target cell expressing appropriate entry receptors. Recent work showed that DC-SIGN are high-affinity binding receptors for HCV. Besides playing a role in entry into DC, HCV E2 interaction with DC-SIGN might also be detrimental for the interaction of DC with T cells during antigen presentation. The clinical strategies that target DC-SIGN may be successful in restricting HCV dissemination and pathogenesis as well as directing the migration of DCs to manipulate appropriate immune responses in autoimmunity and tumorigenic situations.
 ...
PMID:DC-SIGN: binding receptor for HCV? 1505 67

We explored the impact of human ABO glycosyltransferase and Lewis and secretor fucosyltransferase polymorphisms in HIV infection. We found that, compared with healthy blood donors, HIV-infected patients display a significant decrease in Le(a-b+) phenotype frequencies. We showed that HIV binding on DC-SIGN-transduced Jurkat cells was inhibited by fucosyl bovine serum albumin. Our results suggest a slight protective effect of Lewis b antigen on HIV infection, possibly by the competition of Lewis antigens with HIV for binding to DC-SIGN.
AIDS 2005 Mar 24
PMID:Decrease of Lewis frequency in HIV-infected patients: possible competition of fucosylated antigens with HIV for binding to DC-SIGN. 1580 83

We report here the gene sequence for DC-SIGN (CD209) from chimpanzees. DC-SIGN is a C-type lectin expressed by dendritic cells. It is involved in DC-T cell interactions as well as in HIV-1 and SIV transmission. We have cloned two new alleles for chimpanzee DC-SIGN. The coding sequences are highly homologous to the two previously described chimpanzee alleles. We confirm the existence of a polymorphism within the repeat region of DC-SIGN. In humans polymorphisms in the repeat region have been associated with resistance to HIV infection. However, we have not been able to correlate the number of repeats with susceptibility of chimpanzees to HIV infection. The actual impact of DC-SIGN variability in HIV infection therefore remains to be determined.
AIDS Res Hum Retroviruses 2005 Sep
PMID:Chimpanzee DC-SIGN alleles predict the existence of A and B isoforms, but do not support a role for resistance to HIV infection. 1621 8


1 2 3 4 Next >>