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)

CD28 is a transmembrane glycoprotein that provides T cells with an essential co-stimulatory signal during antigen presentation. Using flow cytometry, we document here an expansion of CD28- T cells in HIV infection. Whereas the percentage of CD4+CD28+ T cells among total lymphocytes was decreased, a small increase of the percentage of CD4+CD28- T cells was observed. In the CD8+ subset, there was a marked expansion of CD8+CD28- T cells. An increased percentage of CD8+ T cells positive for HLA-DR was found in both CD28+ and CD28- cells. Results were similar for CD38 expression. HIV infection was also distinguished by a shift from LFA-1lowCD28low to LFA-1highCD28high and LFA-1high-CD28neg expression pattern on CD8+ T cells. Negative correlations were found between percentage and absolute number of CD8+CD28+ T cells and several serum parameters usually associated with poor prognosis (IgA, IgE, beta 2-microglobulin and HIV-1 p24 antigen). Thus, HIV infection is characterized by a marked expansion of CD28- T cells with an abnormal expression of activation markers and cell adhesion molecules. In addition, CD8+CD28+, but not CD8+CD28- or total CD8+ T cell numbers, correlated with the levels of established serological markers of disease severity or progression and may, therefore, have predictive value.
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PMID:Expansion of T cells negative for CD28 expression in HIV infection. Relation to activation markers and cell adhesion molecules, and correlation with prognostic markers. 880 49

During December 1992-January 1993, the Thai Ministry of Public Health collected blood samples from populations at high risk of HIV infection (prostitutes and men attending sexually transmitted disease clinic). All these samples were evaluated for HIV infection by enzyme immunoassay and, if positive, confirmed by the Western blot. There were 141 HIV-1 reactive samples. In a blind study, laboratory personnel of the Venereal Diseases and Control Center in Chonburi, Thailand, later analyzed 586 serum samples with test strips (Sero-Strip HIV; Saliva Diagnostics Systems; Singapore). The strips have a synthetic peptide representing a highly conserved region of viral transmembrane glycoprotein, gp41. This peptide captures HIV-1 antibodies. Three investigators read the test strips independently. There were no discrepant readings among them. The test strips were also evaluated under nonlaboratory conditions of decentralized settings: exposure for 21 weeks at 45 degrees Celsius, exposure for 20 weeks at 22 degrees Celsius, and 98% relative humidity. The results of the test strips correlated completely with those of the conventional immunoassays. Thus, there were neither false positive nor false negative reactions. In conclusion, these test strips can be used reliably in non-air-conditioned tropical settings.
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PMID:Simplified testing for antibodies to human immunodeficiency virus. 881 20

Human immunodeficiency virus type 1 (HIV-1) transmembrane glycoprotein 41 (gp41) contains an immunosuppressive domain (Env amino acids 583-599). Previous studies by us and others using recombinant soluble gp41 (rsgp41; amino acids 539-684) and immunosuppressive peptide (1SP; a gp41 peptide, amino acids 583-599) have shown that HIV-1 gp41 by the immunosuppressive domain could bind to several proteins on human T, B and monocyte cell lines, and also to normal human peripheral blood mononuclear cells. In this study we demonstrated that HIV-1 rsgp41 could inhibit spontaneous cell proliferation of human T cell lines H9 and Jurkat, B cell lines Raji and Daudi, monocyte cell line U937, but could not inhibit cell proliferation of human fibroblast cell line HEF and green monkey kidney cell line Cos-1. HIV-1 rsgp41 could inhibit also concanavalin A (Con A)-, phytohaemagglutinin (PHA)- and tetanus toxoid (TT)-induced cell proliferation of normal human peripheral blood lymphocytes, with 50% inhibition at a concentration of 8 microM, but could not inhibit pokeweed mitogen (PWM)-induced lymphocyte proliferation. Furthermore, recombinant soluble gp36 of HIV-2 like HIV-1 rsgp41 could inhibit Con A-, but not PWM-induced lymphocyte proliferation. These results indicate that HIV-1 gp41-induced inhibition of proliferation is selective in so far as the effect of PWM is not altered while the effects of several other stimuli are.
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PMID:HIV-1 gp41 selectively inhibits spontaneous cell proliferation of human cell lines and mitogen- and recall antigen-induced lymphocyte proliferation. 884 89

Reverse transcription of HIV-1, without detergent or amphipathic peptide-induced permeability of the viral envelope, has been demonstrated to occur in the intact HIV-1 virion. In this report, we demonstrate that the amphipathic domains in the C terminus of the transmembrane glycoprotein (gp41) account for the natural permeability of the HIV-1 envelope to deoxyribonucleoside triphosphates, the substrates for DNA polymerization. In addition, nonphysiological deoxyribonucleoside triphosphates, such as 3'-azido-3'-deoxythymidine 5'-triphosphate and 3'-deoxythymidine 5'-triphosphate, can also penetrate the viral envelope, incorporate into, and irreversibly terminate reverse transcripts. As a result, viral infectivity is potently inhibited. Since the lentiviral envelope with these newly demonstrated characteristics can serve as a delivery pathway for anti-reverse transcription agents, we propose a unique strategy to prevent HIV-1 interand, possibly, intrahost transmission.
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PMID:Amphipathic domains in the C terminus of the transmembrane protein (gp41) permeabilize HIV-1 virions: a molecular mechanism underlying natural endogenous reverse transcription. 890 14

Human CD38 is a nonlineage-restricted type II transmembrane glycoprotein that has emerged as a multifunctional protein in recent years. It can serve as an ectoenzyme that catalyzes the synthesis and hydrolysis of cyclic ADP-ribose, a recently identified Ca2+ mobilizing agent that acts independently of inositol triphosphate. The enzymatic functions of CD38 probably contribute to an array of its immunoregulatory functions. The release of soluble CD38 and the ability of membrane-bound CD38 to become internalized in response to appropriate stimuli suggest that extracellular and intracellular roles for this protein are equally plausible. Ligation of CD38 with agonistic antibodies induces diverse effects in hematopoietic cells that range from growth stimulation to induction and prevention from apoptosis, induction of cytokines, activation of kinases, and phosphorylation of certain proteins. These observations suggest that CD38 may serve as receptor for an as yet unidentified ligand. Other molecules that share significant structural and functional homology to CD38 have been identified in humans and mice, suggesting that these molecules may represent a new family of proteins. Understanding the role of CD38 in certain pathological conditions such as myeloma, X-linked agammaglobulinemia, and HIV infection may provide insight into its physiological functions.
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PMID:Human CD38, a cell-surface protein with multiple functions. 890 11

HIV gp41 is the transmembrane glycoprotein responsible for fusion of viral and cellular membranes, enabling viral entry. The structure of gp41 was studied using two synthetic peptides derived from the ectodomain of gp41: a 38-residue peptide from the "heptad repeat" region (hr.wt), and a 34-residue peptide from a region closer to the C-terminus (bt wt). These peptides were found to form a trimer of heterodimers with approximately 80% alpha-helicity. To study their alignment, distances between spin-labels attached to Cys residues on Cys-substituted peptides were measured using a recently-developed electron paramagnetic resonance method [Rabenstein, M.D., & Shin, Y.-K. (1995) Proc Natl. Acad. Sci. U.S.A. 92, 8239-8243]. The heterotrimeric peptides were found to be antiparallel, consistent with a study on proteolytically cleaved peptide fragments of gp41 [Lu, M., Blacklow, S.C., & Kim, P.S. (1995) Nat. Struct. Biol. 2, 1075-1082]. Furthermore, the C-terminal 19 residues of hr.wt are not apposed to bt.wt, and 15 residues of bt.wt extend beyond the end of br.wt. Consistent with this alignment are tertiary interactions between specific sites of these peptides probed by spin-label mobility. Additionally, a second pair of peptides was studied. From the model, these are expected to align with complete overlap. Alone, neither was helical, but when mixed, they were 83% helical. Based on the alignment of the peptides, a model of the prefusogenic form of gp41 was constructed which is significantly different from the structure of influenza hemagglutinin.
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PMID:HIV-1 gp41 tertiary structure studied by EPR spectroscopy. 890 89

Human immunodeficiency virus type 1 (HIV-1) can readily accept envelope (Env) glycoproteins from distantly related retroviruses. However, we previously showed that the HIV-1 Env glycoprotein complex is excluded even from particles formed by the Gag proteins of another lentivirus, visna virus, unless the matrix domain of the visna virus Gag polyprotein is replaced by that of HIV-1. We also showed that the integrity of the HIV-1 matrix domain is critical for the incorporation of wild-type HIV-1 Env protein but not for the incorporation of a truncated form which lacks the 144 C-terminal amino acids of the cytoplasmic domain of the transmembrane glycoprotein. We report here that the C-terminal truncation of the transmembrane glycoprotein also allows the efficient incorporation of HIV-1 Env proteins into viral particles formed by the Gag proteins of the widely divergent Moloney murine leukemia virus (Mo-MLV). Additionally, pseudotyping of a Mo-MLV-based vector with the truncated rather than the full-length HIV-1 Env allowed efficient transduction of human CD4+ cells. These results establish that Mo-MLV-based vectors can be used to target cells susceptible to infection by HIV-1.
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PMID:Truncation of the human immunodeficiency virus type 1 envelope glycoprotein allows efficient pseudotyping of Moloney murine leukemia virus particles and gene transfer into CD4+ cells. 906 Jul 7

The fusion domain of human immunodeficiency virus (HIV-1) envelope glycoprotein (gp120-gp41) is a conserved hydrophobic region located at the N terminus of the transmembrane glycoprotein (gp41). A V2E mutant has been shown to dominantly interfere with wild-type envelope-mediated syncytium formation and virus infectivity. To understand this phenomenon, a 33-residue peptide (wild type, WT) identical to the N-terminal segment of gp41 and its V2E mutant were synthesized, fluorescently labeled, and characterized. Both peptides inhibited HIV-1 envelope-mediated cell-cell fusion and had similar alpha-helical content in membrane mimetic environments. Studies with fluorescently labeled peptide analogues revealed that both peptides have high affinity for phospholipid membranes, are susceptible to digestion by proteinase-K in their membrane-bound state, and tend to self- and coassemble in the membranes. In SDS-polyacrylamide gel electrophoresis the WT peptide formed dimers as well as higher order oligomers, whereas the V2E mutant only formed dimers. The WT, but not the V2E mutant, induced liposome aggregation, destabilization, and fusion. Moreover, the V2E mutant inhibited vesicle fusion induced by the WT peptide, probably by forming inactive heteroaggregates. These data form the basis for an explanation of the mechanism by which the gp41 V2E mutant inhibits HIV-1 infectivity in cells when co-expressed with WT gp41.
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PMID:Fusion peptides derived from the HIV type 1 glycoprotein 41 associate within phospholipid membranes and inhibit cell-cell Fusion. Structure-function study. 915 94

The env gene of SIV and HIV-1 encodes a single glycoprotein gp 160, which is processed to give a noncovalent complex of the soluble glycoprotein gp120 and the transmembrane glycoprotein gp41. The extracellular region (ectodomain), minus the N-terminal fusion peptide, of gp41 from HIV-1 (residues 27-154) and SIV (residues 27-149) have been expressed in Escherichia coli. These insoluble proteins were solubilized and subjected to a simple purification and folding scheme, which results in high yields of soluble protein. Purified proteins have a trimeric subunit composition and high alpha-helical content, consistent with the predicted coil-coil structure. SIV gp41 containing a double cysteine mutation was crystallized. The crystals are suitable for X-ray structure determination and, preliminary analysis, together with additional biochemical evidence, indicates that the gp41 trimer is arranged as a parallel bundle with threefold symmetry.
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PMID:The extracellular domain of immunodeficiency virus gp41 protein: expression in Escherichia coli, purification, and crystallization. 926 Feb 78

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.
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PMID:Production and characterization of monoclonal antibodies to simian immunodeficiency virus envelope glycoproteins. 928 16


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