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:C0001175 (AIDS)
120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A study by Hall et al. (J Virol 1992;66:2456-2463; Ref. 11) has suggested the existence of two closely related molecular subtypes of HTLV-II, which were tentatively designated HTLV-IIa and HTLV-IIb. To confirm this nucleotide sequence analysis of 986 bp of the env gene region encoding the entire surface glycoprotein, gp46, and the amino terminus of the transmembrane glycoprotein, gp21, of 10 HTLV-II isolates was carried out. The results clearly established the existence of two subtypes and demonstrated a 4.3% divergence in sequence in this region. Analysis of other gene regions of the provirus, including the pol (1544 bp), gag (448 bp), and the entire LTR (743 bp) of two representative isolates of each subtype, showed a sequence divergence of 3.8 to 5.7%, with greatest divergence occurring in the LTR. In addition to single nucleotide changes, the gag regions encoding the structural protein, p19, of the HTLV-IIb isolates were also found to have a 66-bp deletion that would be expected to result in a p19 protein having a 22-amino acid deletion in the carboxy-terminus region. Attempts to exploit this to differentiate the two subtypes serologically were unsuccessful in that recombinant p19 proteins of both subtypes were found to be antigenically cross-reactive. The finding of two molecular subtypes of HTLV-II may have important implications for a better understanding of the biological and pathogenic properties of the virus, and will be useful in characterizing the viruses present in endemic foci in American Indian populations.
AIDS Res Hum Retroviruses 1993 Aug
PMID:Nucleotide sequence analysis of human T cell leukemia virus, type II (HTLV-II) isolates. 821 42

Numerous studies have established the correlation between antibodies to the core protein p24 of HIV-1 and the progression of the acquired immunodeficiency syndrome. In this study, we analyzed the immune response to two recombinant gag proteins, p24 and p17, in order to evaluate their diagnostic or prognostic significance. Immune response to the immunodominant domain of the transmembrane glycoprotein gp41 was used as a reference. Sera collected from individuals from France and Burundi (Central Africa) at various CDC stages of HIV-1 infection were tested using three sandwich enzyme-linked immunoassays developed with a synthetic peptide corresponding to the immunodominant domain of gp41, SP gp41, or recombinant p24 and p17 cloned and expressed in Escherichia coli. These assays allowed detection of titer antibodies to the three cited antigens. Antibodies to SP gp41 were detected in every HIV-1-positive patient from France and Burundi, generally at a high and stable level. Results obtained with p24 confirmed the value of antibodies to p24 as a prognostic marker only in European and North American populations, since the African population had very high levels of these antibodies even at an advanced stage of the disease. They also confirmed that initial antibody response to p24 is more predictive of outcome than antibody titer change over time. Although antibodies to p17 decline during progression to AIDS, they are frequently absent in French patients at early, asymptomatic stages and therefore could not be used as a prognostic marker. In contrast, antibodies to p17 are significantly less common in African patients with AIDS when compared with symptomless HIV-1-infected African individuals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prevalence and persistence of antibody titers to recombinant HIV-1 core and matrix proteins in HIV-1 infection. 831 75

Antigenic variation is a characteristic feature of lentiviral infection. The SIV/macaque model of AIDS provides an ideal system in which to investigate the molecular basis of antigenic variation. The purpose of this study was to genetically map the nucleotide changes in env that alter the neutralization phenotype of SIV. Serum taken from an SIVmac239-infected macaque (2D) at 30 weeks postinoculation was found to neutralize the input virus (SIVmac239) and an isolate, P9, obtained at 10 weeks p.i., but did not neutralize two other isolates, P13 and P23, obtained at 20 and 52 weeks, respectively. Sequence analysis of these virus variants revealed clustered amino acid changes in V1 and single base pair changes in V2-V4 of P13 and P23. Infectious recombinant viruses in which the V1 and V1-V3 sequences of SIVmac239 were replaced with those of P13 or P23 retained the neutralization profile of SIVmac239; both were neutralized by macaque 2D serum. Recombinants containing the entire surface glycoprotein (gp120) (V1-V5) and the 5' portion of gp41 of P13 and P23 and those containing gp120 sequences from V4 through the 5' portion of the transmembrane glycoprotein (gp41) were not neutralized by 2D serum. Using a panel of monoclonal antibodies in radioimmunoprecipitation assays, P23 and recombinants containing V4 and V5 of P23 were shown to be antigenically distinct from P13 and SIVmac239. The majority of the amino acid changes in the antigenically distinct viruses were clustered in V4 (amino acids 413-418) and these changes created new potential N-linked glycosylation sites. This study demonstrates that a small number of specific amino acid changes (amino acids 412 to 418 in the env gene) in the V4 region of the SIV envelope glycoprotein can alter antibody recognition and neutralization and that these phenotypic changes may be associated with altered glycosylation of the envelope.
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PMID:Antigenic variation of SIV: mutations in V4 alter the neutralization profile. 866 10

A potential component that may be useful for passive immunotherapy for HIV-1 is human monoclonal antibodies (HumAbs) possessing potent anti-HIV-1 activity that is directed against conserved regions of the envelope glycoprotein. Such antibodies would, in principle, have the ability to neutralize diverse isolates of HIV-1. To develop such reagents, hybridomas were derived by initial Epstein Barr virus transformation of peripheral blood mononuclear cells (PBMCs) from an asymptomatic HIV-1 seropositive donor followed by fusion with heteromyelomas, and secreted anti-HIV-1 antibodies were further characterized. The specificity of one HumAb, designated as clone 3, was determined by enzyme-linked immunosorbent assay (ELISA) and Western blotting analyses that indicated reactivity to the transmembrane envelope glyco-protein gp41. Synthetic pentadecapeptides overlapping by 10 amino acids were utilized for epitope mapping of clone 3; a decapeptide GCSGKLICTT in the transmembrane gp41 was identified as the epitope. Clone 3 bound to SupT1 cells infected with HTLV-IIIB in fluorescent activated cell sorting analysis. In addition, in vitro biological assays demonstrated that clone 3 possessed neutralization reactivity against diverse laboratory isolates as well as an AZT-resistant isolate. Therefore, clone 3 reactivity defines a conserved neutralizable site on the HIV-1 transmembrane glycoprotein. Clone 3 and the conserved immunogenic epitope on gp41 could be useful in passive and active immunotherapy for the acquired immunodeficiency syndrome (AIDS).
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PMID:A human monoclonal antibody to HIV-1 gp41 with neutralizing activity against diverse laboratory isolates. 867 26

Human CD38 is a transmembrane glycoprotein involved in lymphocyte activation and adhesion to endothelium. The ectocellular domain of the molecule possesses properties of a bifunctional enzyme catalyzing both the synthesis from NAD+ and the hydrolysis of the calcium-releasing metabolite cyclic ADP-ribose (cADPR). Surface expression of CD38 (mCD38) is rapidly and almost completely down-modulated upon ligation by specific mAb in cells from different lineages. The data presented here also show that, in addition to the existence of a mCD38, a soluble form of CD38 (sCD38) is detectable in the cell culture supernatant of allo-activated T lymphocytes and of several tumor cell lines. sCD38 is also present in vivo and is assayable in normal (fetal serum and amniotic fluid) and pathological (serum and ascites from patients with multiple myeloma, and serum from patients with AIDS) biological fluids. Immunoaffinity chromatography, SDS-PAGE and Western blot analyses with mAb and polyclonal antibodies, along with metabolic labeling, yield a body of data concerning the structure of sCD38, which displays a M(r) of 39 kDa. Native sCD38 maintains the ability to inhibit the binding activity of different anti-CD38 mAb and still catalyzes the synthesis and the hydrolysis of cADPR at the same ratio observed with mCD38. Furthermore, cross-linking experiments indicate that the purified soluble molecule binds a 120 kDa molecule expressed by monocytoid cells and identified as a candidate ligand for human mCD38.
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PMID:Identification and characterization of an active soluble form of human CD38 in normal and pathological fluids. 894 58

Twelve monoclonal antibodies (MAbs), TB1 to TB12, were produced against a soluble vaccinia recombinant envelope glycoprotein (gp140) from simian immunodeficiency virus SIVmac251. These MAbs recognized SIV gp140 with a relatively high affinity (K0.5 from 6.7 x 10(-8) to 4 x 10(-9) M). All the MAbs except TB9, TB11, and TB12 cross-reacted with HIV-2 envelope glycoproteins, but none of the 12 MAbs recognized those from HIV-1. Using a panel of 87 overlapping synthetic peptides containing 20 amino acid residues, with an overlap of 10 amino acids and spanning the entire primary sequence of gp140, 3 linear epitopes were identified. The first mapped with a neutralizing MAb, TB12, which recognized a linear sequence around amino acids 28-31 within the N-terminal end of the external envelope glycoprotein. The two other new nonneutralizing MAbs recognized linear epitopes around amino acid sequence 380-381 by MAbs TB1, TB2, and TB3, and at the transmembrane glycoprotein amino acids 581-600 by MAb TB6. Seven of the 12 MAbs, TB4, TB5, TB7-9, TB10, and TB11, failed to bind the linear synthetic peptides in ELISA. Moreover, among these seven MAbs only MAbs TB4, TB5, TB9, and TB10 failed to recognize SIV envelope glycoproteins in Western blot (WB) or ELISA after reduction of disulfide bridges by dithiothreitol (DTT), suggesting that they are directed against conformational or discontinuous epitopes. It is of interest to note that MAb TB10 can block the binding of gp140 to the CD4 receptor when the MAb is previously incubated with gp140. Consistent with this result, MAb TB10 cannot bind to gp140 that has been previously complexed with the CD4 receptor. All these results suggest that MAb TB10 recognizes a conformational or discontinuous epitope overlapping or close to the CD4-binding site. These properties are probably implicated in the neutralizing activity observed with this MAb.
AIDS Res Hum Retroviruses 1997 Sep 01
PMID:Production and characterization of monoclonal antibodies to simian immunodeficiency virus envelope glycoproteins. 928 16

The carboxy-terminal 29 amino acids of the human immunodeficiency virus type 1 transmembrane glycoprotein (HIV-1 TM) are referred to as lentivirus lytic peptide 1 (LLP-1). Synthetic peptides corresponding to LLP-1 have been shown to induce cytolysis and to alter the permeability of cultured cells to various small molecules. To address the mechanisms by which LLP-1 induces cytolysis and membrane permeability changes, various concentrations of LLP-1 were incubated with Xenopus laevis oocytes, and two-electrode, voltage-clamp recording measurements were performed. LLP-1 at concentrations of 75 nM and above induced dramatic alterations in the resting membrane potential and ionic permeability of Xenopus oocytes. These concentrations of LLP-1 appeared to induce a major disruption of plasma membrane electrophysiological integrity. In contrast, concentrations of LLP-1 of 20-50 nM induced changes in membrane ionic permeability that mimic changes induced by compounds, such as the bee venom peptide melittin, that are known to form channel-like structures in biological membranes at sublytic concentrations. An analog of LLP-1 with greatly reduced cytolytic activity failed to alter the electrophysiological properties of Xenopus oocytes. Thus, by altering plasma membrane ionic permeability, the carboxy terminus of TM may contribute to cytolysis of HIV-1-infected CD4+ cells.
AIDS Res Hum Retroviruses 1997 Nov 20
PMID:A synthetic peptide corresponding to the carboxy terminus of human immunodeficiency virus type 1 transmembrane glycoprotein induces alterations in the ionic permeability of Xenopus laevis oocytes. 939 Jul 52

Recent advances in the quantitative assessment of viral burden, by permitting the extension of criteria applied to assess the efficacy of vaccines from all-or-none protection to diminution of the viral burden, may allow the identification of original immunogens of value in combined vaccines. Peptides corresponding to three domains of the envelope glycoproteins of feline immunodeficiency virus that are recognized during natural infection were used to immunize cats. After challenge with a primary isolate of feline immunodeficiency virus, the development of acute infection was monitored by quantitative assessment of the viral burden in plasma and tissues by competitive reverse transcription-PCR, by measurement of the humoral response developed to viral components, and by lymphocyte subset analysis. Whereas immunization with two peptides derived from the surface glycoprotein had no effect on the early course of infection, immunization with a peptide derived from the transmembrane glycoprotein delayed infection, as reflected by a diminished viral burden in the early phase of primary infection and delayed seroconversion. This peptide, located in the membrane-proximal region of the extracellular domain, has homology to an epitope of human immunodeficiency virus type 1 recognized by a broadly neutralizing monoclonal antibody. These results suggest that lentivirus transmembrane glycoproteins share a determinant in the juxtamembrane ectodomain which could be of importance in the design of vaccines against AIDS.
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PMID:Delayed infection after immunization with a peptide from the transmembrane glycoprotein of the feline immunodeficiency virus. 949 1

Contrary to earlier reports, we have found that tri- and hexapeptides analogous or homologous with segments of the 23-residue N-terminal fusion sequence (FS) of the viral transmembrane glycoprotein gp41 (residues 517-539) did not significantly inhibit HIV-1-induced syncytium formation, using an uninfected cell-infected cell fusion assay. In contrast, we found that the high molecular weight apolipoprotein A-1 and a 23-residue analog of the FS, with the phenylalanine residues at positions 524 and 527 replaced with alanine residues, were effective inhibitors. Although the tripeptides were ineffective as inhibitors of syncytium formation, we found a number of them inhibited red cell lysis induced by the synthetic peptide AVGIGALFLGFLGAAGSTMGARS (based on the HIV-1 gp41 FS). This effect was also seen with apolipoprotein A-1. The Ala524,527 analog of the fusion sequence could not be tested in this system because it was hemolytic. We concluded that the smaller peptides were effective inhibitors of hemolysis because they interfered with pore formation by the fusion sequence peptide, either by disrupting the pores or by preventing the peptide from adopting the alpha-helical conformation found in the pores. On the other hand, membrane fusion, which is a prelude to syncytium formation, has been shown to require the fusion sequence in the beta-strand conformation. We argue that small peptides would be unable to block interaction between such strands, although larger molecules, such as apolipoprotein A-1 and the Ala524,527 analog, would be able to do so and thus inhibit fusion. It seems, therefore, that a successful drug directed against the FS-cell membrane interaction stage of syncytium formation would need to be of relatively high molecular weight and complexity.
AIDS Res Hum Retroviruses 1998 Mar 20
PMID:Efficacy of fusion peptide homologs in blocking cell lysis and HIV-induced fusion. 954 97

The association between antibody reactivity to the neutralizing epitope ELDKWA in the transmembrane glycoprotein gp41 and disease progression was investigated in 29 children perinatally infected with HIV-1. Levels of antibody reactivity to this epitope, measured over time, were associated with absolute CD4+ lymphocyte numbers and disease status, and inversely associated with the levels of acid-dissociated p24 antigen in the plasma. Early virus isolates from 10 of 12 children with no detectable antibody reactivity to this epitope were sequenced. Only three contained sequences that differed from the consensus, indicating that this epitope is well conserved in this population. None of these three children developed antibodies to the autologous sequences, indicating that at least 80% of children with negative antibody reactivity to this epitope were true nonresponders. Together, these results indicate that the ELDKWA determinant could be an important component in the formulation of a vaccine or for immunotherapeutic approaches to HIV-1 infection.
AIDS Res Hum Retroviruses 1998 May 01
PMID:Association of antibody reactivity to ELDKWA, a glycoprotein 41 neutralization epitope, with disease progression in children perinatally infected with HIV type 1. 959 12


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