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)

CD4 is a transmembrane glycoprotein of the immunoglobulin superfamily, expressed on developing thymocytes, major histocompatibility class II (class II MHC) restricted mature T lymphocytes and, in humans, on cells of the macrophage/monocyte lineage. On lymphoid cells, CD4 plays a critical role during thymocyte ontogeny and in the function of mature T cells. CD4 binds to non-polymorphic regions of class II MHC acting as a co-receptor for the T-cell antigen receptor (TCR). It increases avidity between thymocytes and antigen-presenting cells and contributes directly to signal transduction through association with the Src-like protein tyrosine kinase p56lck. Its precise role on monocytes and macrophages is unclear. CD4 is also a co-receptor for the human and simian immunodeficiency viruses (HIV-1, HIV-2 and SIV). Clinically, CD4 antibodies may be used to achieve immunological tolerance to grafts and transplants.
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PMID:CD4: a co-receptor in the immune response and HIV infection. 930 2

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.
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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

The transmembrane glycoprotein gp41 of HIV-1 contains a C1q binding domain (HIVenv 583-610) and activates the human complement system through the classical pathway. Based on structural and functional similarities between human defensins (human neutrophil peptide, HNP 1-3) and synthetic peptides representing the env 583-610 region of HIV-1, we found it interesting to investigate the C1q binding and complement activating ability of human defensins. Human defensins were purified and characterized by size exclusion chromatography, ultrafiltration, gel electrophoresis and HPLC. The complement activating ability of the purified peptides was assessed in a solid-phase immunoassay. Defensins, fixed to an ELISA plate, were able to bind the C1q subcomponent of the first complement component (C1), triggering the classical pathway of complement activation which led to C4b binding to the plate. Reduction and subsequent alkylation of disulfide bridges of defensins greatly decreased the C1q binding ability but complement activation (C4b binding) remained high. Further acetylation of the reduced defensin peptide resulted in a molecule which bound very little or no C1q but still activated the complement cascade. These phenomena indicate that defensins interact with the complement system via C1q-dependent and C1q-independent mechanisms, and extend the number of functional similarities between defensins and gp41 of HIV-1 to include C1q binding and complement activation.
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PMID:Defensins purified from human granulocytes bind C1q and activate the classical complement pathway like the transmembrane glycoprotein gp41 of HIV-1. 944 79

The effect of extracellular domain of human immunodeficiency virus (HIV-1) transmembrane glycoprotein gp41 on interleukin (IL)-10, IL-2, interferon (IFN)-y, IL-4, and tumor necrosis factor-alpha production by human peripheral blood mononuclear cells (PBMC) was assessed by ELISA. Rapid gp41-induced increase of IL-10 production was detected in resting PBMC and isolated monocytes but not in B, T, or NK cells. Furthermore, gp41 also enhanced IL-10 production in staphylococcal enterotoxin B-stimulated PBMC, while synthesis of IL-2, IFN-gamma, and IL-4 in these cells was down-modulated. Kinetic studies revealed that increased IL-10 production preceded reduction of IL-2, indicating the possible IL-10 regulatory role in the gp41-induced down-modulation of this cytokine. Anti-IL-10 antibody reversed almost completely the gp41 inhibitory effect on IL-2 production. In this study, HIV-1 gp41 was a potent modulator of cytokine production by PBMC, in particular by increasing IL-10 secretion from normal monocytes/macrophages and consequently down-regulating IL-2 and IFN-gamma.
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PMID:gp41 envelope protein of human immunodeficiency virus induces interleukin (IL)-10 in monocytes, but not in B, T, or NK cells, leading to reduced IL-2 and interferon-gamma production. 953 62

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.
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PMID:Efficacy of fusion peptide homologs in blocking cell lysis and HIV-induced fusion. 954 97

In view of our recent findings that a truncated form of the envelope (Env) glycoprotein of human immunodeficiency virus type 1 (HIV-1) was efficiently incorporated into MoMLV particles, we studied the generation of Moloney murine leukemia virus (MoMLV)/simian immunodeficiency virus (SIV) pseudotypes. Unlike HIV-1, both the wild-type SIV Env and a truncated form, which lacks most of the cytoplasmic domain of the transmembrane glycoprotein, were incorporated into MoMLV particles and generated infectious retroviral vectors which could transduce CD4+ sMAGI macaque cells. The infection depended on target cell CD4 expression, and was neutralized by both soluble CD4 and sera from SIV-infected macaques. We also observed pseudotype-mediated gene transfer of a green fluorescent protein marker into the CD4+ CEMX174 and C8166 lymphoid cell lines. More importantly, primary human lymphocytes were also successfully transduced ex vivo by MoMLV/SIV pseudotypes, albeit at lower efficiency, and gene transfer was specifically restricted to the CD4+ subset. These findings demonstrate that MoMLV/SIV pseudotypes can be used to transduce cells which are susceptible to SIV infection, and thus might be advantageously employed in animal models for direct in vivo delivery of gene therapy-based approaches.
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PMID:Pseudotyping of Moloney leukemia virus-based retroviral vectors with simian immunodeficiency virus envelope leads to targeted infection of human CD4+ lymphoid cells. 957 40

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.
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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

The presence of antibodies able to enhance infection in vitro in sera from human immunodeficiency virus (HIV)-1-infected patients raises the possibility that antibodies exert a deleterious activity during natural infection. The anti-HIV-1 humoral response and plasma HIV-1 RNA were measured in a cohort of 98 infected mothers, included in the French Prospective Study on Pediatric HIV Infection, 49 of whom transmitted HIV to their children. Transmission from mother to child was associated with antibody responses to the envelope gp160 (P = .009 for serum dilution of 1/400) and to a highly conserved domain of the transmembrane glycoprotein (P = .055 for serum dilution of 1/400) and with plasma HIV-1 RNA levels (P < .0001). Multivariate logistic regression indicated that a high anti-gp160 response and a high plasma virus load are independent risk factors for perinatal transmission of HIV-1 (odds ratio, 3.4; 95% confidence interval, 1.1-9.9 for anti-gp160; odds ratio, 2.8; 95% confidence interval, 1.6-5.0 for virus load).
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PMID:Apparent enhancement of perinatal transmission of human immunodeficiency virus type 1 by high maternal anti-gp160 antibody titer. 960 61

Perturbation of astrocyte functions by HIV-1 infection may contribute to the pathogenesis of AIDS dementia complex (ADC). The present study investigated the possibility that astroglial transport of glutamate and aspartate, the major excitatory amino acids (EAAs) in the mammalian central nervous system (CNS), is altered by HIV-1 infection. Human U251 glioma cells were infected with the brain isolate SF162 of HIV-1. HIV-1 persisted in glial cells over several months. This nonproductive infection of glial cells was characterized by persistent expression of Nef over the time of the infection, and the transient presence of structural viral proteins, including the viral transmembrane glycoprotein gp41, which was detected during the initial 2 weeks following HIV-1 infection. The presence of gp41 in acutely HIV-1-infected glial cells coincided with a 36% decrease in D-[3H]aspartate uptake, owing to a reduction in the maximal transport capacity (vmax) for D-aspartate. The expression of typical astrocytic glutamate transporters EAAT1 and EAAT2 in U251 glioma cells was not altered by HIV-1 infection. To determine whether viral protein gp120, gp41, or Nef was involved in the impairment of EAA transport in acutely HIV-1-infected glial cells, effects of lentiviral lytic peptide type 1 (LLP-1) (corresponding to the carboxy terminus of gp41), recombinant SF2 gp120, and recombinant LAI Nef on D-[3H]aspartate uptake and the release of glutamate in glial cells were investigated. Only LLP-1 reduced D-[3H]aspartate uptake and facilitated the release of glutamate from glial cells in a concentration-dependent manner. These results suggest that the carboxy terminus of gp41 impairs EAA transport in glial cells, which may contribute to excitotoxic damage to neurons in HIV-1 infection of the CNS.
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PMID:Impairment of excitatory amino acid transport in astroglial cells infected with the human immunodeficiency virus type 1. 978 74

Ebola virions contain a surface transmembrane glycoprotein (GP) that is responsible for binding to target cells and subsequent fusion of the viral and host-cell membranes. GP is expressed as a single-chain precursor that is posttranslationally processed into the disulfide-linked fragments GP1 and GP2. The GP2 subunit is thought to mediate membrane fusion. A soluble fragment of the GP2 ectodomain, lacking the fusion-peptide region and the transmembrane helix, folds into a stable, highly helical structure in aqueous solution. Limited proteolysis studies identify a stable core of the GP2 ectodomain. This 74-residue core, denoted Ebo-74, was crystallized, and its x-ray structure was determined at 1.9-A resolution. Ebo-74 forms a trimer in which a long, central three-stranded coiled coil is surrounded by shorter C-terminal helices that are packed in an antiparallel orientation into hydrophobic grooves on the surface of the coiled coil. Our results confirm the previously anticipated structural similarity between the Ebola GP2 ectodomain and the core of the transmembrane subunit from oncogenic retroviruses. The Ebo-74 structure likely represents the fusion-active conformation of the protein, and its overall architecture resembles several other viral membrane-fusion proteins, including those from HIV and influenza.
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PMID:Core structure of the envelope glycoprotein GP2 from Ebola virus at 1.9-A resolution. 1007 67


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