Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0021051 (immunodeficiency)
71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new, modular Western blot (immunoblot) system for human immunodeficiency virus (HIV) antibodies (ABN WesPage; Wellcome) was compared with enzyme immunoassays (Wellcome, Behringwerke, and Abbott) and with a U.S. Food and Drug Administration (FDA)-licensed Western blot (DuPont) in a multicenter study. A total of 649 serum samples from HIV patients at different stages of the disease, as well as from high-risk patients, from patients with conditions unrelated to AIDS, and from healthy blood donors, were used in the evaluation along with nine seroconversion panels. For evaluation of Western blot reactivity, both Centers for Disease Control (CDC) and FDA criteria were used. With the DuPont Western blot as the reference assay, the overall sensitivity and specificity of the ABN WesPage were 100 and 99.1%, respectively, when indeterminate results were not taken into account and when both tests were interpreted in accordance with CDC criteria. The DuPont Western blot detected significantly more antibodies to pol and gag gene products than the ABN WesPage. The ABN WesPage showed a higher positive rate of detection of viral envelope band gp160. When both Western blots were interpreted in accordance with CDC criteria, the ABN WesPage and the DuPont Western blot yielded 9.3 and 10.4% indeterminate results, respectively. When the DuPont Western blot was interpreted in accordance with the manufacturer's instructions (FDA criteria), 25.7% of the samples tested were regarded as indeterminate. The choice of interpretation criteria is of paramount importance for the evaluation of HIV Western blot patterns.
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PMID:Multicenter evaluation of the novel ABN Western blot (immunoblot) system in comparison with an enzyme-linked immunosorbent assay and a different Western blot. 155 87

The binding of the human immunodeficiency virus envelope glycoprotein gp120 to the CD4 molecule is the initial step in the viral replicative cycle. This interaction is therefore an important target for therapeutic intervention for the treatment of human immunodeficiency virus infection. We designed an enzyme-linked immunosorbent assay which detects the interaction between recombinant soluble forms of CD4 and gp160. This assay could be used as an initial screen of libraries of synthetic chemical compounds and natural products.
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PMID:Simple assay to screen for inhibitors of interaction between the human immunodeficiency virus envelope glycoprotein and its cellular receptor, CD4. 160 91

The external envelope glycoprotein (gp120) of the human immunodeficiency virus (HIV) has been shown to be toxic to neurons in culture. To further investigate the neurological effects of gp120, the involvement of this protein with the acquisition of spatial discrimination was assessed. Both native and recombinant gp120 were administered into the cerebral ventricles of adult rats and performance was evaluated in the Morris swim maze. Gp120 treatment retarded acquisition after daily administration of 12 ng. The specificity of this impairment was demonstrated in that the performance of animals given the same amount of gp160 from recombinant baculovirus was not different from animals given saline. Vasoactive intestinal peptide (VIP) has been shown to block gp120-induced neurotoxicity in culture and a VIP receptor antagonist has displayed toxic properties to neurons in culture. We show here that this antagonist, which competitively inhibits VIP binding and blocks VIP-mediated functions in cell cultures from the CNS, also produced an impairment of performance. This retardation was attenuated by cotreatment with VIP, supporting the specificity of the observed impairment. Thus, gp120 and the VIP antagonist produced similar retardation of spatial discrimination, suggesting that both may impair memory for spatially related stimulus control.
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PMID:Learning impairment following intracerebral administration of the HIV envelope protein gp120 or a VIP antagonist. 161 29

Polyclonal B-cell activation is a characteristic feature of AIDS and of the AIDS-related complex. Since the immunoregulatory cytokine interleukin-6 (IL-6) plays a major role in inducing B-cell differentiation, we examined the effects of native human immunodeficiency virus type 1 envelope glycoproteins gp120 and gp160 on IL-6 induction. In this study, we have demonstrated that both gp120 and gp160 have the ability to induce IL-6 mRNA and biologically active IL-6 protein secretion in peripheral blood mononuclear cells in vitro. The envelope protein preparations had no detectable endotoxin as tested by the Limulus amebocyte lysate assay, and hence we can rule out the effect of contaminating endotoxin, which is a potent inducer of IL-6 in monocyte/macrophage cell cultures. In addition, we have shown that the envelope glycoproteins act directly on CD4(+)-cloned T cells to induce IL-6 production in the absence of monocytes. These findings indicate that monocytes and T cells both contribute to the secretion of IL-6, which plays an important role in the pathogenesis of B-cell activation in human immunodeficiency virus infection.
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PMID:Human immunodeficiency virus type 1 envelope glycoproteins gp120 and gp160 induce interleukin-6 production in CD4+ T-cell clones. 165 94

In a randomised phase I trial of a recombinant vaccina virus vaccine expressing the gp160 envelope gene of the human immunodeficiency virus (HIVAC-1e) 35 healthy, HIV-seronegative males, 31 of whom had a history of smallpox immunisation and 4 of whom were vaccinia naive, were vaccinated and then boosted 8 weeks later with HIVAC-1e or standard NY strain vaccinia virus. The frequency, duration, and titre of virus isolation from the vaccination site and occurrence of local side-effects were similar between the two groups of vaccinees. Vaccinia-naive (vac-n) subjects shed virus from the vaccination site for longer and at a higher titre than did vaccinia-primed (vac-p) individuals (19 vs 7 days and 10(7) vs 10(5) pfu/ml, respectively). In-vitro T-cell proliferative responses to one or more HIV antigen preparations developed in 13 of 16 vaccinia-primed subjects inoculated with HIVAC-1e. T-cell responses were, however, transient and in no subject did antibodies to HIV become detectable. The 2 vaccinia-naive subjects vaccinated with HIVAC-1e showed strong T-cell responses to homologous and heterologous strains of whole virus and to recombinant gp160 protein that remained detectable for over a year; antibodies to HIV envelope also developed in both. Recombinant vaccinia virus vaccines induce T-cell priming to the foreign gene products in most individuals. If used as the sole immunising agent they will be most efficacious in vaccinia-naive individuals.
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PMID:Safety of and immunological response to a recombinant vaccinia virus vaccine expressing HIV envelope glycoprotein. 167 28

The presence of anti-CD4 antibodies in sera of human immunodeficiency virus (HIV)-seropositive individuals has been recently documented, but its origin remains unknown. To test the hypothesis that anti-idiotypic antibodies to gp120, the HIV envelope glycoprotein with high affinity for CD4, mimic the configuration of gp120 and bind CD4, we performed two sets of experiments. First, we tested the possibility that anti-CD4 antibodies present in sera of a proportion of HIV-positive individuals exhibit variable region complementarity to autologous anti-gp120 antibodies. We show here that affinity-purified human anti-gp160 antibodies recognize specifically autologous affinity-purified anti-CD4 antibodies. We also demonstrate that antibodies to CD4 competitively inhibit anti-gp160 autologous antibodies binding to gp160. This implies that at least some anti-CD4 antibodies are directed towards idiotypic motifs located on anti-gp120 antibodies and that they may result from an anti-idiotypic response to anti-gp120 antibodies. In a second set of experiments, we examined the effect of anti-idiotypic immunization of experimental animals against human anti-gp120 antibodies. We found that anti-idiotypic antibodies produced in a rabbit immunized against affinity-purified human anti-gp120 antibodies specifically recognize recombinant and cellular human CD4, and that this interaction is competitively inhibited by soluble CD4. The data support the concept of idiotypic mimicry whereby anti-idiotypic antibodies produced against anti-gp120 antibodies recognize CD4, the cellular receptor of HIV.
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PMID:Anti-idiotypic antibodies to human anti-gp120 antibodies bind recombinant and cellular human CD4. 167 46

In the present study inactivated human immunodeficiency virus type 1 (HIV-1) was conjugated to Brucella abortus and tested for immunogenicity in normal and anti-L3T4-treated BALB/c mice. HIV-BA was more immunogenic than uncoupled HIV in normal mice, since 6-fold less virus in HIV-BA preparations elicited higher titer responses than HIV-1 alone. Furthermore, the HIV-BA antibody response reached higher levels before the HIV-1 response. Immunoblot analysis showed that most of the HIV-1 antigens were recognized by antibodies induced by either HIV-1 or HIV-BA. Isotype analysis revealed that HIV-1 induced similar levels of IgG1 and IgG2a antibodies, whereas the IgG2a responses to HIV-BA were more pronounced than the IgG1 response. These different IgG subclass patterns suggest that conjugation of HIV-1 to BA changed the immunogenic nature of HIV-1. The requirement for helper T cells was examined by immunizing mice that were depleted of CD4+ T cells by in vivo anti-L3T4 treatment. Under these conditions the IgG responses to HIV-1 were completely eliminated. Although HIV-BA antibody responses were markedly reduced in anti-L3T4-treated mice, anti-HIV-1 antibodies, mainly of the IgG2a isotype, were produced. The antibodies generated by HIV-1 and HIV-BA immunization were also tested for their ability to inhibit syncytia formed by infecting CD4 + CEM cells with gp160 vaccinia. Sera from normal mice, immunized with either HIV-1 or HIV-BA were capable of inhibiting syncytia. In contrast, following anti-L3T4 treatment, only mice immunized with HIV-BA, but not HIV-1, produced antibodies capable of inhibiting syncytia.
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PMID:Production of a novel antigen by conjugation of HIV-1 to Brucella abortus: studies of immunogenicity, isotype analysis, T-cell dependency, and syncytia inhibition. 167 17

Apparently conflicting results have been reported regarding the role of env glycoprotein glycans in human immunodeficiency virus type 1 (HIV-1) infectivity and cytopathogenicity. Whereas we have shown that enzymic removal of carbohydrates from mature envelope glycoproteins has only limited effect on the ability of HIV-1 to bind to CD4 and to infect target cells, sugar analogues that interfere with the glycosylation process of the nascent molecule markedly reduce virus infectivity. Here we have investigated the effect of a glucosidase inhibitor, 1-deoxynojirimycin (dNM), on the bioactivity and immunoreactivity of precursor gp160 produced by recombinant vaccinia virus-infected BHK-21 cells (rgp160). dNM (4 mM) did not affect the amount of rgp160 recovered nor its secretion from the cells. As described by other authors the effect of dNM was incomplete, resulting in the production of rgp160, the glycosylation of which was heterogeneous with respect to apparent Mr distribution and to sensitivity to endoglycosidase H and endoglycosidase F, all the species being susceptible to N-glycanase. A major reduction of the binding to CD4+ cells was noted with rgp 160 produced by dNM-treated cells using a quantitative indirect immunofluorescence assay and labelling with polyclonal human anti-HIV IgG. Similarly, dNM treatment altered the accessibility to murine monoclonal antibody 110-4 of the exposed V3 loop of HIV-1 gp120 by at least 10-fold, as determined by either ELISA capture assay or immunoaffinity purification. Such bioactivity and conformation modifications, which result from the abnormal folding of the nascent glycoprotein due to aberrant glycosylation, may account for the impaired HIV-1 infectivity elicited by dNM.
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PMID:Effect of a glucosidase inhibitor on the bioactivity and immunoreactivity of human immunodeficiency virus type 1 envelope glycoprotein. 167 78

A mouse monoclonal anti-idiotypic antibody (anti-Id), designated MC1, was generated against chimpanzee antibodies specific for a synthetic peptide corresponding to a native epitope associated with gp41 of human immunodeficiency virus (HIV). This anti-Id recognized a shared idiotope/idiotype (Id) on a second chimpanzee anti-gp41 peptide preparation but failed to detect this Id on rabbit and mouse anti-gp41 peptide antibodies induced by immunization with the gp41 synthetic peptide. The chimpanzee Id-MC1 reaction was not inhibited by either synthetic peptide or recombinant gp160 suggesting that MC1 exhibits noninternal image, Ab-2 alpha-like characteristics. Immunization of syngeneic Balb/c mice with MC1 induced an antigen-positive (Ag+) response capable of binding the synthetic peptide, recombinant gp160, and gp41, whereas MC1-immunized rabbits did not produce any detectable anti-peptide and/or anti-HIV envelope glycoprotein antibody response. The MC1-induced anti-Id response (Ab-3) in both mice and rabbits expressed a similar Id with the Ab-1, which is not normally expressed in the anti-gp41 peptide antibody response induced by the nominal antigen in Balb/c mice and in rabbits. Together, these studies indicate that a mouse monoclonal anti-Id of the Ab-2 alpha class can induce an anti-HIV response specific for a gp41 epitope defined by a synthetic peptide, which does not cross species barriers.
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PMID:Administration of noninternal image monoclonal anti-idiotypic antibodies induces idiotype-restricted responses specific for human immunodeficiency virus envelope glycoprotein epitopes. 168 76

A human Epstein-Barr virus-transformed lymphoblastoid B-cell line was generated from peripheral blood mononuclear cells (PBMC) of an asymptomatic human immunodeficiency virus type I (HIV-1) seropositive donor, which produces a human monoclonal antibody K14 (IgG1), reactive with an epitope on the transmembrane part (gp41) of the envelope glycoprotein of HIV-1. This monoclonal antibody reacts with a lysate of HIV-1-infected H9 cells, gradient purified HIV-1, and a vaccinia recombinant HIV-1 gp160 protein, but not with HIV-2 antigens in an enzyme-linked immunosorbent assay (ELISA). When used as an immobilized ligand in an immune affinity column, K14 selectively purifies gp41 from a HIV-1-infected H9 cell lysate. Although no reactivity was observed in ELISA with a panel of partially overlapping synthetic nonapeptides spanning the whole length of HIV-1 gp41, it was shown to react with recombinant envelope proteins, provided that they did contain amino acids 643-692: deletion of this part resulted in the disappearance of the reactivity. Testing of an extensive panel of the sera from HIV-1 seropositive or seronegative donors from Europe and Africa, including a selected group of donors before and after HIV-1 seroconversion, in a competition ELISA with horseradish peroxidase-conjugated K14, showed that the epitope recognized on gp41 is immunodominant and conserved. K14 does not neutralize HIV-1 infectivity or virus-mediated cell fusion, and does not mediate antibody-dependent cellular cytotoxicity.
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PMID:Production and characterization of a human monoclonal antibody, reactive with a conserved epitope on gp41 of human immunodeficiency virus type I. 169 24


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