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)

A panel of 20 recombinant Fab fragments reactive with the surface glycoprotein gp120 of human type 1 immunodeficiency virus (HIV-1) were examined for their ability to neutralize MN and IIIB strains of the virus. Neutralization was determined as the ability of the Fab fragments to inhibit infection as measured in both a p24 ELISA and a syncytium-formation assay. One group of closely sequence-related Fab fragments was found to neutralize virus in both assays with a 50% neutralization titer at approximately 1 micrograms/ml. Another Fab neutralized in the p24 ELISA but not in the syncytium assay. The other Fab fragments showed weak or no neutralizing ability. The results imply that virion aggregation or crosslinking of gp120 molecules on the virion surface is not an absolute requirement for HIV-1 neutralization. Further, all of the Fab fragments were shown to be competitive with soluble CD4 for binding to gp120 and yet few neutralized the virus effectively, implying that the mechanism of neutralization in this case may not involve receptor blocking. The observation of a preponderance of high-affinity Fab fragments with poor or no neutralizing ability could have implications for vaccine strategies.
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PMID:Recombinant human Fab fragments neutralize human type 1 immunodeficiency virus in vitro. 138 50

Two acute phase reactants, four cytokines, five soluble factors and lymphocyte subpopulations have been simultaneously evaluated in 16 subjects before and closely after the HIV-Ab seroconversion time. The same variables have also been determined in 50 HIV-Ab-negative high risk subjects, in 36 CDC II-III and in 30 CDC IV patients, utilizing a mixed longitudinal epidemiological model. The results show significant variations of few parameters in the early phases (increase: sCD8, beta-2-Microglobulin, sIL-2R, sCD23, Neopterin, IFN-alpha; decrease: CD4+ lymphocytes). In the course of the disease, many others parameters progressively increase (IFN-tau, IL-4, IL-6, acid-alpha 1-glycoprotein, alpha 1-antitrypsin) or decrease (B- and T-lymphocytes). Ferritin, in particular, highly increases only in CDC IV stage. These data may be useful to monitor patients during the entire course of their disease and to suggest the time elapsed from seroconversion.
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PMID:Behaviour of several 'progression markers' during the HIV-Ab seroconversion period. Comparison with later stages. 138 75

We previously described a significant sequence homology between HIV-1 gp120 and the functional sites responsible for the specific binding of snake curare-mimetic neurotoxins and rabies virus glycoprotein to the nicotinic acetylcholine receptor. Here we report findings about the existence of a mechanism of functional molecular mimicry which could enable the binding of HIV-1 gp120 to nicotinic acetylcholine receptors in muscle cells and neurons.
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PMID:Binding of HIV-1 gp120 to the nicotinic receptor. 139 97

We describe a new method for the transfer of carbohydrate moieties to polypeptides in which complex carbohydrate, in the form of glycosyl amino acid, is removed from an available glycoprotein, derivatized, and reacted with a polypeptide via an iodoacetylated alpha-amino group. A family of oligomannose chains, N-linked to the side chain of Asn, was obtained from ovalbumin by pronase digestion and purified as previously described. A reactive sulfhydryl group was specifically placed on these molecules by reaction of 2-iminothiolane with the Asn alpha-amino group. Separately, the alpha-amino group of the peptide GGYR was specifically iodoacetylated by reaction with iodoacetic anhydride at pH 6. Reaction of the thiol-containing carbohydrate with iodoacetylated peptide at pH 8 gave in high yield the corresponding oligomannosyl-peptides, whose structures were confirmed by mass spectrometry. A peptide inhibitor of HIV protease was also oligomannosylated by this procedure. The principle advantage of this method is the efficiency of the reaction even when performed with stoichiometric amounts of the two molecules at low concentration. It should be feasible to extend this chemistry to larger polypeptides.
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PMID:A novel method for the incorporation of glycoprotein-derived oligosaccharides into neoglycopeptides. 142 Apr 38

Sulfation is a posttranslational modification of proteins which occurs on either the tyrosine residues or the carbohydrate moieties of some glycoproteins. In the case of secretory proteins, sulfation has been hypothesized to act as a signal for export from the cell. We have shown that the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein precursor (gp160) as well as the surface (gp120) and transmembrane (gp41) subunits can be specifically labelled with 35SO42-. Sulfated HIV-1 envelope glycoproteins were identified in H9 cells infected with the IIIB isolate of HIV-1 and in the cell lysates and culture media of cells infected with vaccinia virus recombinants expressing a full-length or truncated, secreted form of the HIV-1 gp160 gene. N-glycosidase F digestion of 35SO4(2-)-labelled envelope proteins removed virtually all radiolabel from gp160, gp120, and gp41, indicating that sulfate was linked to the carbohydrate chains of the glycoprotein. The 35SO42-label was at least partially resistant to endoglycosidase H digestion, indicating that some sulfate was linked to complex carbohydrates. Brefeldin A, a compound that inhibits the endoplasmic reticulum to Golgi transport of glycoproteins, was found to inhibit the sulfation of the envelope glycoproteins. Envelope glycoproteins synthesized in cells treated with chlorate failed to incorporate 35SO42-. However, HIV glycoproteins were still secreted from cells in the presence of chlorate, indicating that sulfation is not a requirement for secretion of envelope glycoproteins. Sulfation of HIV-2 and simian immunodeficiency virus envelope glycoproteins has also been demonstrated by using vaccinia virus-based expression systems. Sulfation is a major determinant of negative charge and could play a role in biological functions and antigenic properties of HIV glycoproteins.
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PMID:Sulfation of the human immunodeficiency virus envelope glycoprotein. 143

X-ray quality crystals of an Fab fragment from an antipeptide monoclonal antibody (R/V3-50.1) that recognizes the principal neutralizing determinant (PND) of the gp120 glycoprotein of human immunodeficiency virus type 1 (HIV-1) (MN isolate) were grown as uncomplexed and peptide complexed forms. Crystals of the free Fab grew from high salt in orthorhombic space groups P2(1)2(1)2(1) and I222 and from polyethylene glycol in space groups P1 and P2(1). Seeds from either the P1 and P2(1) native (uncomplexed) Fab crystals induced nucleation of crystals of the Fab complexed to a 16-residue synthetic peptide corresponding to the PND when streak seeded into preequilibrated solutions of this complex. Data were collected from these complex crystals and from each of the four native Fab forms to at least 2.8 A resolution. The genes for the variable domain of the Fab were cloned and sequenced and the primary amino acid sequence was deduced from this information. Knowledge of the three-dimensional structure of this Fab-peptide complex will be important in the understanding of the PND of HIV-1 and its recognition by neutralizing monoclonal antibodies.
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PMID:Crystallization, sequence, and preliminary crystallographic data for an antipeptide Fab 50.1 and peptide complexes with the principal neutralizing determinant of HIV-1 gp120. 143 87

In order to examine the potential role of env-induced membrane fusion in the cytopathogenic properties of HIV-1 in cell culture, the effects of mutations within the proteolytic cleavage site of gp160, which result in a reduction but not a complete absence of proteolytic processing have been further studied. Cells expressing the mutant glycoproteins were shown to be severely reduced in their capacity to form syncytia. However, viruses encoding these glycoproteins could infect cell culture cells, albeit with delayed kinetics, and, at late infection time points, resulted in complete cytolysis of the infected culture. Since amplification by polymerase chain reaction and direct sequencing of the DNA in the infected cultures confirmed the presence of the mutant and the absence of revertant DNA, this shows that the amount of fusion competent viral glycoprotein does not influence HIV-1 cytopathogenicity, but rather that other parameters must be involved in inducing cell death.
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PMID:HIV-1-induced cytopathogenicity in cell culture despite very decreased amounts of fusion-competent viral glycoprotein. 145 94

Among the retroviruses, the surface (SU) and transmembrane (TM) glycoproteins of lentiviruses are linked exclusively by noncovalent bonds. For some C-type retroviruses, however, a small proportion of the SU proteins has been shown to be linked to their TM proteins by a disulfide bond, with the remainder being noncovalently associated. A region near the carboxyl terminus of the HIV-1 SU glycoprotein has been implicated in contacting the TM glycoprotein. Computer modelling indicates that this region of divergent lentivirus and oncovirus SU glycoproteins forms a structurally conserved "pocket" which could accommodate a "knob"-like protrusion formed by an immunodominant region in the TM protein containing the CxxxxxC (lentiviruses) or CxxxxxxCC (C- and D-type viruses) motif. An anti-idiotypic monoclonal antibody, raised against a monoclonal antibody reacting with a sequence in the "pocket" of HIV-1 gp120, was found to bind to synthetic peptides close to the CxxxxxC motif. It is suggested that part of the SU-TM linkage mechanism for the lentiviruses and oncoviruses is a 'knob and socket' structure and that the interaction between SU and TM proteins is similar in one region for lentiviruses and C-type as well as D-type viruses. The conserved knob and socket linkage may be relevant to a mechanism for viral-cell membrane fusion that is broadly common to all of these retroviruses.
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PMID:Conserved structural features in the interaction between retroviral surface and transmembrane glycoproteins? 145 3

Mutations within the principal neutralizing determinant (the V3 loop) of the HIV-1 surface envelope glycoprotein gp120 block or greatly reduce the ability of the HIV-1 envelope glycoprotein to induce cell fusion in CD4+ HeLa T4 cells while keeping its CD4 binding ability. However, when either cysteine or both cysteines forming the V3 disulfide bridge were mutated, the resultant glycoprotein could not mediate cell fusion, undergo proteolytic processing, or bind CD4. To investigate the role that the V3 loop plays in gp160 processing and CD4 binding, we deleted the entire V3 loop region of the HIV-1 env gene. The resultant glycoprotein could not mediate cell fusion in the HeLa T4 cell line and no proteolytic processing of gp160 or CD4 binding could be detected. To test whether any domain of the V3 loop is involved in attaining the proper envelope glycoprotein conformation required for proteolytic processing and CD4 binding, we introduced a series of deletions into the coding region of the V3 loop. Most of the residues within the V3 loop could be removed while retaining gp160 processing and CD4 binding. Our results indicate that the cysteines that form the V3 loop or the disulfide bond itself are important for proper envelope glycoprotein folding and processing. Because many of the mutants constructed in this study do not contain the type-specific neutralizing determinant of HIV-1, they may be potential reagents to bind group-specific neutralizing antibodies or to elicit a group-specific neutralizing response against HIV-1.
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PMID:Studies on the role of the V3 loop in human immunodeficiency virus type 1 envelope glycoprotein function. 145 7

We describe a peptide vaccine model containing a built-in adjuvant. This model used a multiple antigen peptide system (MAPS) to amplify peptide antigens and a lipoamino acid, tripalmitoyl glyceryl cysteine (P3C), as a built-in adjuvant. An 18-residue peptide antigen (B2) derived from the third variable domain (amino acid 312-329) of the glycoprotein gp120 of type I human immunodeficiency virus (HIV-1) was used in this model. This peptide antigen is a suitable target since it consists of neutralizing, T-helper, and T-cytotoxic epitopes. The peptide antigen in a tetravalent MAPS format (B2M-P3C) with a lipophilic attachment was synthesized by two routes for comparison: a direct stepwise approach and an indirect modular approach. In the stepwise approach, each residue was sequentially added to the peptide resin to give B2M-P3C and the P3C was incorporated to the side chain of a carboxyl terminal lysine as Fmoc-Lys(P3C). In the modular approach, a module containing a chloroacetylated core matrix of MAPS (M-P3C) with a carboxyl tetrapeptide bearing Lys(P3C) and a second module containing the peptide antigen B2 with a cysteine at its terminus were synthesized and purified separately, and then coupled to each other to form B2M-P3C. In the modular approach, the molecular ion of B2M-P3C was unambiguously identified by ion-spray mass spectrometry. B2M-P3C, administered in liposomes without any adjuvant such as Freund's complete adjuvant, was used to immunize mice and found to induce gp120-specific antibodies in vitro, and prime cytotoxic T lymphocytes in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A rational design of synthetic peptide vaccine with a built-in adjuvant. A modular approach for unambiguity. 147 79


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