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

HIV-1 infects the brain and leads to AIDS dementia complex. The viral coat glycoprotein, gp120, may facilitate the passage of HIV-1 and HIV-infected immune cells across the blood-brain barrier (BBB). Since the endothelial cells of the BBB do not possess the CD4 or galactosylceramide binding sites used by gp120 to induce HIV-1 uptake into other cell types, how gp120 mediates entry into brain is unknown. We postulate that gp120 crosses the BBB and does so by acting as a weak lectin to induce adsorptive endocytosis (AE) in a fashion similar to other glycoproteins like wheatgerm agglutinin (WGA). We found in vivo that gp120 crosses the BBB and its passage is enhanced 18.7-fold by WGA. In vitro studies confirm that WGA enhances uptake of gp120 by brain endothelia; most of the uptake is membrane-associated, as expected in AE. Uptake is not dependent on clatharin, caveolae, calcium channels, or endosomal acidification. Our results suggest that gp120 crosses the BBB and does so by acting as a lectin to induce AE.
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PMID:HIV-1 protein gp120 crosses the blood-brain barrier: role of adsorptive endocytosis. 928 88

The lectin jacalin was shown to specifically stimulate CD4(+) lymphocytes. This lectin, which presents a peptide highly similar to a sequence of the HIV external glycoprotein, interacts with CD4 and is able to inhibit in vitro HIV infection. Since jacalin binds also CD8, its mitogenic specificity cannot exclusively be attributed to its interaction with CD4. We therefore hypothesized that the lectin could trigger signals specifically associated with CD4. Here we show that jacalin triggers IL2 gene transcription only in CD4(+) lymphocytes. In parallel, we show that numerous proteins are tyrosine phosphorylated in this cell subset while only a restricted number of them are phosphorylated in CD8(+) cells. Moreover, we show that the tyrosine kinase p56lck, which is associated with both CD4 and CD8, is activated only in CD4(+) lymphocytes, making this lectin a good model for the study of cell signaling triggered in this restricted subpopulation.
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PMID:The lectin jacalin specifically triggers cell signaling in CD4+ T lymphocytes. 934 92

In previous studies, we have demonstrated that O-glycans at the surface of HIV-1-infected cell lines were hyposialylated. Moreover, we and others have shown that HIV+ individuals produced autoantibodies that react with hyposialylated CD43, on T cell lines. Since the autoantigen responsible for this abnormal immune response was not easily found in the peripheral blood cells of corresponding patients, we searched for its possible presence in other sites. Using fluorescence staining of alveolar macrophages with various lectins, we show that the binding of the PNA lectin specific for asialo O-glycans is much more efficient on cells from HIV-1-infected individuals. Moreover, the degree of reactivity of PNA is correlated with the clinical stage of the illness.
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PMID:Altered sialylation of alveolar macrophages in HIV-1-infected individuals. 935 44

Neurological dysfunction is not uncommon in patients suffering from acquired immunodeficiency syndrome (AIDS) and, when manifested, intimates involvement of the central nervous system. Here, the human immunodeficiency virus (HIV) infects preferentially microglial cells, which thereby release substances known to interfere with neuronal function. One class of agents set free in this manner are proteases; these degrade certain components within, and thereby undermine the integrity of, the extracellular matrix (ECM) compartment, which plays a vital role in cell-to-cell communication. We wished to ascertain whether the ECM compartment is indeed disrupted in the brains of AIDS victims. We examined the neocortical areas of 27 AIDS autopsy cases, including 9 with diagnosed HIV-encephalopathy (HIVE); 8 HIV-seronegative cases with various types of brain lesion, including viral infections, were also included in this study. HIV-antigens and DNA were identified by use of immunohistochemistry and in situ hybridization, and ECM components by lectin staining and immunohistochemistry. Of the 27 AIDS cases examined, each of the 9 with HIVE was completely devoid of labeled ECM components; 8 of the 18 without HIVE had incurred substantial losses, and only 2 manifested a normal complement of constituents within this compartment. With respect to stratal and topographic variations, layers II and III were less affected than layers V to VII, as was the frontal cortex relative to other areas. These findings confirmed our expectations of the brain's ECM undergoing degradation following HIV infection, and these changes may well underlie the neurological disturbances manifested in AIDS patients.
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PMID:HIV-I induced destruction of neocortical extracellular matrix components in AIDS victims. 936 7

Phosphatidylserine (PtdSer) is synthesized by an exchange of the polar head group of phospholipids for a serine residue. The enzyme responsible for this reaction, the serine-base exchange enzyme system (serine-BEES) is inhibited during lymphocyte activation. We show here that triggering the CD4 cell surface molecule in several CD4+ T-cell lines regulates the serine-BEES activity, thus resulting in marked changes in PtdSer synthesis. CD4 ligands able to generate an activating signal in T-cells such as the lectin jacalin, down-regulate the synthesis of PtdSer. In contrast, monoclonal antibodies (mAbs) directed against the CD4 molecule, such as IOT4 and IOT4a, which have previously been described as generating an inhibitory signal to T-cells, induced an up-regulation of the serine-BEES and impaired CD3-induced inhibition of PtdSer synthesis. Similarly, the HIV-gp120 envelope glycoprotein, in both soluble and cross-linked forms, induces an increase in PtdSer synthesis. The protein tyrosine kinase p56lck participates in the regulation of serine-BEES activity because the effect of CD4 mAbs was additive to that of amino-hydroxyflavone, an inhibitor of p56lck. Also, CD4 mAbs were inactive in J Cam 1.6 cells or when the CD3 signals were bypassed by using thapsigargin. These results demonstrate that the CD4 surface molecule can transmit both activating and inhibiting intracellular signals depending on the CD4 ligand used. We suggest that PtdSer synthesis would be one of the intracellular signals that could explain the opposite effects of different CD4 ligands on T-cells.
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PMID:Regulation of the serine-base exchange enzyme system by CD4: effects of monoclonal antibodies, jacalin, interleukin 16 and the HIV membrane protein gp120. 940 74

A lectin such as concanavalin A (Con A) was immobilized on the surfaces of poly(methacrylic acid) branches covered with polystyrene nanospheres with a diameter of 360 nm, which were obtained by the free radical copolymerization of styrene with the poly(tert-butylmethacrylate) macromonomer, followed by hydrolysis. Using Con A-immobilized (0.3 microgram/cm2) nanospheres, the interaction of the nanospheres with HIV-1 was determined by the reduction of the gp120 level and the viral infectivity of the HIV-1 suspensions after a 60 min incubation at room temperatures. Con A-immobilized nanospheres achieved a 95 and a 77% reduction of the gp120 level and the infectivity at a concentration of 0.5 mg/mL, respectively, indicating the effective capture of the gp120 and the virions.
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PMID:Capture of HIV-1 gp120 and virions by lectin-immobilized polystyrene nanospheres. 946 May 46

Cell-free human immunodeficiency virus type 1 (HIV-1) can be taken up and released by a monolayer of primary human gingival cells and remain infectious for CD4+ cells. Virus-sized latex particles covalently coated with purified native HIV-1 envelope glycoprotein gp120 are also transported through the primary epithelial cells. This process is significantly stimulated by increasing the intracellular cyclic AMP (cAMP) concentration. Inhibition experiments with mannan and alpha-methyl-mannopyranoside indicated that mannosyl groups are involved in the interaction between gp120 and gingival cells. An increase of cellular oligomannosyl receptors by incubation with the mannosidase inhibitor deoxymannojirimycin augmented transcellular transport of the gp120-coated particles. The results suggest that infectious HIV can penetrate gingival epithelia by a cAMP-dependent transport mechanism involving interaction of the lectin-like domain of gp120 and mannosyl residues on glycoproteins on the mucosal surface. Penetration of HIV could be inhibited by soluble glycoconjugates present in oral mucins.
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PMID:Epithelial uptake and transport of cell-free human immunodeficiency virus type 1 and gp120-coated microparticles. 955 12

Peripheral blood dendritic cells (DC) produce IFN-alpha in response to challenge by many enveloped viruses including herpes simplex virus (HSV) and HIV, whereas Sendai virus predominantly stimulates IFN-alpha production by monocytes. Glycosylated viral envelope proteins are known to be important for the induction of IFN-alpha. In this study we demonstrate that stimulation of IFN-alpha synthesis by HSV is inhibited by a number of monosaccharides, including fucose, N-acetylglucosamine, and N-acetylgalactosamine as well as the yeast polysaccharide mannan, supporting a role for lectin(s) in the IFN-alpha stimulation pathway. Furthermore, antiserum to the mannose receptor (MR) also inhibited HSV, vesicular stomatitis virus, and HIV-induced IFN-alpha production, but failed to inhibit the IFN-alpha induced by Sendai virus. We further demonstrated that freshly isolated blood DC and IFN-alpha-producing cells responding to HSV stimulation express the MR. This study therefore implicates the MR as an important receptor for the nonspecific recognition of enveloped viruses by DC and the subsequent stimulation of IFN-alpha production by these viruses. Thus, the MR probably serves as a critical link between innate and adaptive immunity to viruses, especially given the role of the MR in Ag capture by DC and the importance of IFN-alpha in shaping immunity.
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PMID:The mannose receptor mediates induction of IFN-alpha in peripheral blood dendritic cells by enveloped RNA and DNA viruses. 972 35

Mannose-binding lectin (MBL) is the most intensively studied human collectin. It is recognized to be a versatile macro-molecule with many of the functional characteristics of IgM, IgG and Clq. In the presence of calcium the protein can bind to a wide spectrum of oligosaccharides through multiple lectin domains. Such binding to the repeating sugar arrays on microbial surfaces may result in direct uptake by one or more collectin receptors on phagocyte surface or may trigger the activation of a pro-serine protease complex (MASP 1 and MASP 2) leading to cleavage of C4 and C2 of the classical complement pathway. Although serum levels of MBL are normally rather low (1500 micrograms/litre) there is increasing evidence that the protein plays an important role in immune defence, particularly during the phase of primary contact with a microorganism. This is suggested by the observed association of an increased incidence of infections in individuals with structural mutations in exon 1 of the MBL gene. A cluster of such mutations in codons 52, 54 and 57 lead to secondary structural abnormalities of the collagenous triple helix and a failure to form biologically functional higher order oligomers. The codon 54 mutation has been identified in several Eurasian populations whereas the codon 57 mutation is characteristic of sub-Saharan populations. One intriguing paradox arising from the MBL genotyping studies is the observation that in many populations there are surprisingly high frequencies of either the codon 54 or codon 57 mutation, suggesting that there may be some biological advantage associated with absence of the protein. Nevertheless, various groups have reported either low serum levels of MBL or an increased frequency of the structural gene mutations in patients with suspected immunodeficiencies, those with frequent unexplained infections and those with systemic lupus erythematosus. There is also evidence that the rate of progression of AIDS in HIV positive men is faster in those with such mutations. A recently published study of a consecutive series of admissions to a paediatric unit suggests that children presenting with an infectious aetiology are significantly more likely to have a MBL mutation. Moreover, this association was independent of age. Prospective studies are underway to address the questions raised by these findings.
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PMID:Mannose-binding lectin (MBL) in health and disease. 977 16

The viral coat of the HIV-1 virus, gp120, has been shown to cross the blood-brain barrier (BBB) in lectin-like fashion by inducing adsorptive endocytosis (AE), a vesicular mechanism that could provide pathways into and across brain endothelial cells for virus and infected immune cells. Here, we extended those findings to show that gp120 slowly crossed the BBB with about 0.15% of an intravenously injected dose entering the brain after about 2 hr. The plant lectin glycoprotein wheat germ agglutinin (WGA) greatly enhanced gp120 crossing without disrupting the BBB. WGA enhanced the uptake of gp120 into all peripheral tissues studied, but the greatest percent increase occurred for brain, whereas another barrier tissue, the testis, had the least increase. Five other plant lectins tested had little or no effect on gp120 uptake by brain, suggesting a key role for sialic acid and N-acetyl-beta-D-glucosaminyl acid, the sugars to which WGA binds, in the uptake of gp120 by brain endothelial cells. WGA did not enhance the uptake of nonglycosylated gp120 and the uptake of gp120 was not self-inhibitable or altered by pretreatment of mice with aluminum. In conclusion, these studies show that gp120 crosses the BBB by a lectin-like mechanism resembling AE that is likely mediated by binding to specific sugar moieties and is rather selective for brain.
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PMID:Characterization of lectin-mediated brain uptake of HIV-1 GP120. 982 62


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