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

We have recently demonstrated that human immunodeficiency virus type 1 (HIV-1) recombinant envelope glycoprotein precursor gp160 (rgp160) behaves as a mannosyl/N-acetylglucosaminyl (GlcNAc) binding protein. If such a carbohydrate-binding property were of biological relevance it should be shared by other related primate immunodeficiency viruses such as HIV-2. The present study confirms this hypothesis and extends these findings by showing that HIV-2 recombinant gp140 (rgp140) specifically interacts with three affinity matrices substituted by synthetic or natural carbohydrate structures: D-mannose-divinylsulphone-agarose, para-aminophenyl-beta-D-GlcNAc-agarose and the natural glycoprotein, bovine fetuin, also coupled to agarose. Binding of rpg140 to the matrices was inhibited by alpha-D-Man17-BSA (where BSA is bovine serum albumin), beta-D-GlcNAc47-BSA and fetuin, and by glycopeptides derived from pronase-treated porcine thyroglobulin. Glycopeptides obtained after endoglycosidase H treatment of thyroglobulin had a limited inhibitory effect, whereas beta-D-Gal17-BSA and beta-D-glucan had no effect. These results indicate that, like HIV-1 envelope glycoprotein, HIV-2 rgp140 interacts with high-mannose and with the mannosyl core of complex-type N-linked glycans, as well as with the N-acetylglucosaminyl core of oligosaccharidic structures.
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PMID:Mannosyl/N-acetyl-beta-D-glucosaminyl binding properties of the envelope glycoprotein of human immunodeficiency virus type 2. 128 Oct 21

Recognition of viral Ag and of the envelope glycoprotein of HIV (gp120) in particular by human Th cells is critical in the immune response to the viral Ag which includes antibody production and generation of cytotoxic cells. Procedures to increase antigenicity of gp120 are highly desirable in a vaccine perspective. Therefore, to induce activation of gp120-specific T cells by a liminal dose of Ag we enhanced uptake of gp120 by exploiting the galactose receptors on APC. Terminal sialic acid residues were removed by neuraminidase treatment from the carbohydrate side chains of the heavily glycosylated gp120. Galactose residues were exposed and hence recognized by galactose receptors on APC. The experiments demonstrated that 1) human monocytes and dendritic cells, but not cells of the B lineage, bear galactose receptor; 2) galactose receptors are indeed involved because enhanced presentation is inhibited by galactose and acetylgalactosamine and competed for by other asialoglycoproteins; 3) galactose receptors mediate internalization of Ag in intracellular compartments that intersect the processing and presenting pathways, resulting in activation of specific T cells; 4) antigenicity of gp120 for specific T cells can be enhanced by the exposure of galactose residues.
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PMID:Galactose receptors and presentation of HIV envelope glycoprotein to specific human T cells. 131 6

A series of four mannose(Man)-, three N-acetylglucosamine (GlcNAc)n-, ten N-acetylgalactosamine/galactose(GalNAc/Gal)-, one 5-acetylneuraminic acid (alpha-2,3-Gal/GalNAc)- and one 5-acetylneuroaminic acid(alpha-2,6-Gal/Gal-NAc)-specific plant agglutinins were evaluated for their antiviral activity in vitro. the mannose-specific lectins from the orchid species Cymbidium hybrid (CA), Epipactis helleborine (EHA) and Listera ovata (LOA) were highly inhibitory to human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) in MT-4, and showed a marked anti-human cytomegalovirus (CMV), respiratory syncytial virus (RSV) and influenza A virus activity in HEL, HeLa and MDCK cells, respectively. The 50% effective concentration (EC50) of CA and EHA for HIV ranged from 0.04 to 0.08 micrograms/ml, that is about 3 orders of magnitude below their toxicity threshold (50% inhibitory concentration for MT-4 cell growth: 54 to 60 micrograms/ml). Also, the (GlcNAc)n-specific lectin from Urtica dioica (UDA) was inhibitory to HIV-1-, HIV-2-, CMV-, RSV- and influenza A virus-induced cytopathicity at an EC50 ranging from 0.3 to 9 micrograms/ml. The GalNAc/Gal-, alpha-2,3-Gal/GalNAc- or alpha-2,6-Gal/GalNAc-specific lectins were not inhibitory to HIV or CMV at non-toxic concentrations. CA, EHA and UDA proved to be potent inhibitors of syncytium formation between persistently HIV-1- and HIV-2-infected HUT-78 cells and CD4+ Molt/4 (clone 8) cells (EC50: 0.2-2 micrograms/ml). Unlike dextran sulfate, the plant lectins CA, EHA and UDA did not interfere with HIV-1 adsorption to MT-4 cells and RSV- and influenza A virus adsorption to HeLa and MDCK cells, respectively. They presumably interact at the level of virion fusion with the target cell.
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PMID:The mannose-specific plant lectins from Cymbidium hybrid and Epipactis helleborine and the (N-acetylglucosamine)n-specific plant lectin from Urtica dioica are potent and selective inhibitors of human immunodeficiency virus and cytomegalovirus replication in vitro. 132 50

Obstetrician-gynecologists and chemists analyzed data on midcycle cervical mucus samples from normally cycling women attending the infertility clinic at the University Hospital of South Manchester, England, to determine the ability of nonoxynol-9 to diffuse into the mucus, thereby testing its spermicidal activity. They used the double diffusion test. They compared diffusion depths of radiolabelled nonoxynol-9 at 120 minutes with those of D-glucose, an uncharged small molecule. They compared the depths of these 2 methods with those of controls containing Tyrode's solution. Migration of spermatozoa in 6 nonoxynol-9 rectangular capillaries was greater than the Tyrode controls, lower in 5 capillaries, and the same in 9 capillaries. Thus, no difference in spermatozoal penetration into midcycle cervical mucus existed between nonoxynol-9 and Tyrode's solution. Further, a 62% concentration of D-glucose was evident in the 1st 5 mm of the cervical mucus column at 2 hours and the concentration fell exponentially. The chemists cold still detect D-glucose at 30 mm at 2 hours. On the other hand, they detected nonoxynol-9 at a 6 times lower concentration than D-glucose in the 1st 5 mm at 2 hours, but could not detect it beyond 5 mm. This meant that, in vivo, only 10% of nonoxynol-9 would be in the interfacial zone of the cervical mucus and not at greater depths. If these results hold true, the ability of nonoxynol-9 to act as a contraceptive and a means to destroy HIV would be limited in the upper genital tract and the cervix. In conclusion, nonoxynol-9's spermicidal activity in midcycle cervical mucus is considerably lower than it is in free solution.
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PMID:Compatibility between the spermicide nonoxynol 9 and mid-cycle human cervical mucus. 133 87

A two-site sandwich fluorescent-ELISA was optimized for the detection of HIV-1 p24 antigen produced by lymphoid cells infected with HIV-1 in vitro. To improve the sensitivity of the ELISA, a combination of streptavidin-beta-galactosidase and a fluorogenic substrate (4-methylumbelliferyl-beta-D-galactopyranoside) was employed for the enzymatic detection stage. Using recombinant p24 as standard antigen, a two-step assay detected as little as 0.7 pg/ml (3.10(-14) M) with an upper limit of 10,000 pg/ml. This detection range (approx. 50-70-times greater than ELISAs using a chromogenic detection) permitted an accurate and straightforward quantitation of p24 in culture supernatants. Overall, the fluorescent-ELISA had increased detectability, sensitivity and efficiency over existing ELISAs for HIV-1 p24.
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PMID:Development of a sensitive ELISA for HIV-1 p24 antigen using a fluorogenic substrate for monitoring HIV-1 replication in vitro. 143 56

Characterization of a polyclonal antibody to galactosyl ceramide (Gal-Cer) which inhibits the internalization and infection of HIV-1 in neural cell lines was carried out. Polyclonal antibody to Gal-Cer was produced by injecting rabbits with Gal-Cer liposomes. The specificity of anti-Gal-Cer binding was studied by high performance thin layer chromatography (HPTLC)-based immunoassay. Using natural and semisynthetic lipids, the specificity of anti-Gal-Cer interaction was studied. The antibody bound to Gal-Cer and its derivatives. The antibody did not bind to glucosyl ceramide or lactosyl ceramide. Glucosyl ceramide differs from Gal-Cer by a hydroxyl group at the fourth carbon and in lactosyl ceramide galactose is linked to ceramide by an intervening glucose molecule. This indicates that D-galactose linked to ceramide is essential for binding. Removal of fatty acid from Gal-Cer, as seen with N-palmitoyl- and N-oleoyl Gal-Cer, had no effect on the binding. It appears that the third carbon of Gal-Cer is not involved in the binding. This is supported by the binding of anti-Gal-Cer to sulfatide or GM4 in which sulfate or sialic acid are added at the third carbon of Gal-Cer, respectively.
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PMID:Galactose to ceramide linkage is essential for the binding of a polyclonal antibody to galactosyl ceramide. 146 87

In order to study the structure-activity relationships of dioxolane nucleosides as potential anti-HIV agents, various enantiomerically pure dioxolane-pyrimidine nucleosides have been synthesized and evaluated against HIV-1 in human peripheral blood mononuclear cells. The enantiomerically pure key intermediate 8 has been synthesized in nine steps from 1,6-anhydro-D-mannose (1), which was condensed with 5-substituted pyrimidines to obtain various dioxolane-pyrimidine nucleosides. Upon evaluation of these compounds, cytosine derivative 19 was found to exhibit the most potent anti-HIV agent although it is the most toxic. The order of anti-HIV potency was as follows: cytosine (beta-isomer) greater than thymine greater than cytosine (alpha-isomer) greater than 5-chlorouracil greater than 5-bromouracil greater than 5-fluorouracil derivatives. Uracil, 5-methylcytosine, and 5-iodouracil derivatives were found to be inactive. Interestingly, alpha-isomer 20 showed good anti-HIV activity without cytotoxicity. As expected, other alpha-isomers did not exhibit any significant antiviral activity. (-)-Dioxolane-T was 5-fold less effective against AZT-resistant virus than AZT-sensitive virus.
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PMID:Asymmetric synthesis of 1,3-dioxolane-pyrimidine nucleosides and their anti-HIV activity. 159 54

The lectin-like protein analogous to bovine conglutinin was purified from human serum. The carbohydrate-binding ability of conglutinin-like protein was inhibited by D-mannose, N-acetylglucosamine and L-fucose as well as by mannan-containing oligosaccharides. By applying a lectin-based ELISA system it was demonstrated that conglutinin-like protein binds to human immunodeficiency virus-1 (HIV-1) glycoprotein 120 (gp120) via its carbohydrate binding site. In vitro experiments with T-lymphoblastoid CEM cells revealed that conglutinin-like protein abolishes infection by HIV-1; a 50% cytoprotective concentration of 23.9 micrograms/ml was measured. These findings demonstrate that human conglutinin-like protein binds to HIV-gp120 and inhibits, under the described in vitro conditions, CEM cell infection.
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PMID:Inhibition of human immunodeficiency virus-1 infection by human conglutinin-like protein: in vitro studies. 161 96

The alpha-(1-3)-D-mannose- and alpha-(1-6)-D-mannose-specific agglutinins (lectins) from Galanthus nivalis, Hippeastrum hybrid, Narcissus pseudonarcissus, and Listera ovata inhibited infection of MT-4 cells by human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) and simian immunodeficiency virus at concentrations comparable to the concentrations at which dextran sulfate (molecular weight, 5,000 [DS-5000]) inhibits these viruses (50% effective concentration, 0.2 to 0.6 microgram/ml). Unlike DS-5000, however, the plant lectins did not inhibit the replication of other enveloped viruses, except for human cytomegalovirus (50% effective concentration, 0.9 to 1.6 microgram/ml). The plant lectins suppressed syncytium formation between persistently HIV-1- or HIV-2-infected HUT-78 cells and uninfected MOLT-4 (clone 8) cells at concentrations that were 5- to 10-fold lower than that required for DS-5000. Unlike DS-5000, however, the plant lectins did not inhibit HIV-1 binding to CD4+ cells. Combination of the plant lectins with DS-5000 led to a potent synergistic inhibition of HIV-1-induced cytopathogenicity in MT-4 cells and syncytium formation between HIV-infected HUT-78 cells and MOLT-4 cells. Our data suggest that alpha-(1-3)-D- and alpha-(1-6)-D-mannose-specific plant lectins interfere with an event in the HIV replicative cycle that is subsequent to the attachment of the virions to the cells (i.e., the fusion process).
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PMID:Alpha-(1-3)- and alpha-(1-6)-D-mannose-specific plant lectins are markedly inhibitory to human immunodeficiency virus and cytomegalovirus infections in vitro. 164 7

The aim of this study was to determine whether mannosyl-specific lectins, especially Concanavalin A (ConA), may bridge HIV-1 env glycoproteins to cell membranes to increase virus binding to its targets, and to what extent this lectin-carbohydrate interaction can modify HIV-1 infectivity for monocytic compared with lymphoid cells. Monocytic U937 and lymphoid CEM cells, which both express surface mannose, were utilized. Whether first incubated with env glycoprotein or with the cells, lectins bound both to the cells and to radiolabeled recombinant gp160 (rgp160). Thus, they enhanced rgp160 adsorption to the cells in a methyl-alpha-mannose inhibitable manner. ConA did not appear to bind to the V1 domain of CD4 at the U937 cell surface since Leu3a binding was not blocked in the presence of ConA, nor was recombinant CD4 retained on a ConA-agarose affinity matrix. Moreover, enhanced rgp160 binding to the cells was CD4 independent, since it was not modified by preincubating the cells with Leu3a. Finally, ConA did not inhibit the binding of CD4-IgG3 chimeric molecules to virions immobilized on nitrocellulose membrane, which argues against the possibility that it interferes with the interaction of gp120 and CD4. However, both when incubated with the virus or with the cells and despite mediating enhanced binding of env glycoprotein, ConA neutralized HIV-1 infectivity for monocytic U937 as well as for lymphoid CEM cells. In this respect, ConA behaves like neutralizing antibodies which do not interfere with CD4 binding of gp120 but rather with some later event that leads to virus entry. These findings obtained with plant lectins may be of relevance in vivo, inasmuch as endogenous mannosyl-binding proteins, which are known to function as opsonins, have been reported to inhibit in vitro infection by HIV-1.
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PMID:Lectin-carbohydrate interactions and infectivity of human immunodeficiency virus type 1 (HIV-1). 173 38


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