Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human immunodeficiency virus (HIV-1) isolates from 8 Ethiopian and 8 Swedish AIDS patients, none of them treated with antiviral drugs, were compared for sensitivity to azido-deoxy-thymidine (AZT), dideoxy-inosine (ddI) and interferon-alpha. HIV was isolated from peripheral blood mononuclear class, identified by Western blot and nucleotide sequencing, and passaged 1-3 times. Sensitivity to the 3 drugs, expressed as ED50s relative to positive controls, was determined by culturing HIV in the presence of drugs in a range of concentrations and assaying the supernatant for p24 antigen and the virus pellet for reverse transcriptase (RT). Dose-dependent anti-HIV activity for AZT was seen in the 8 Ethiopian isolates, and ED50s for p24 antigen and RT activity were correlated. 1 Ethiopian HIV isolate was sensitive to ddI, and another, to interferon-alpha. 1 Swedish HIV was resistant to AZT, and on analysis had a mutation from threonine to tyrosine at position 215. There were no significant differences between ED50s for interferon in the Swedish and Ethiopian HIVs. Combined data for each drug showed correlation between the p24 antigen and RT activities of the Ethiopian and Swedish HIVs. Since there was no resistance observed in the Ethiopian HIV to AZT or ddI, low-dose treatment would probably slow progression of HIV infection in Ethiopians, if these drugs could be made available for clinical trials.
 ...
PMID:Response of Ethiopian human immunodeficiency virus type 1 isolates to antiviral compounds. 128 93

The ability of HIV-1 envelope glycoprotein gp120 to induce transmembrane signaling processes in human T cells and tumor T-cell lines was investigated. Differently glycosylated gp120 preparations were characterized with respect to their purity, the fraction of native gp120, and the affinity of the gp120-CD4 interaction. These data were used to establish experimental conditions that allow a substantial fraction of the CD4 receptor to be complexed with gp120 in the course of the experiments. The results are in contrast to several previous studies since no effect of gp120 on the intracellular Ca2+ concentration, the metabolism of inositol phosphates and arachidonic acid, protein kinase C translocation, and tyrosine phosphorylation was found. Cross-linking of the gp120:CD4 complex by anti-gp120 antibodies did not elicit additional effects.
 ...
PMID:The HIV-1 surface protein gp120 has no effect on transmembrane signal transduction in T cells. 132 56

Human immunodeficiency virus (HIV-1) infection in the human brain leads to characteristic neuropathological changes, which may result indirectly from interactions of the envelope glycoprotein gp120 with neurons and/or glial cells. We therefore investigated the binding of recombinant gp120 (rgp120) to human neural cells and its effect on intracellular signalling. Here we present evidence that rgp120, besides binding to galactocerebroside or galactosyl-sulfatide, specifically binds to a protein receptor of a relative molecular mass of approximately 180,000 Da (180 kDa) present on the CD4-negative glioma cells D-54, but not on Molt4 T lymphocytes. Binding of rgp120 to this receptor rapidly induced a tyrosine-specific protein kinase activity leading to tyrosine phosphorylation of 130- and 115-kDa proteins. The concentration of intracellular calcium was not affected by rgp120 in these cells. Our data suggest a novel signal transducing HIV-1 gp120 receptor on CD4-negative glial cells, which may contribute to the neuropathological changes observed in HIV-1-infected brains.
 ...
PMID:HIV-1 gp120 receptor on CD4-negative brain cells activates a tyrosine kinase. 136 Jan 81

Nevirapine, a dipyridodiazepinone, is a highly specific inhibitor of HIV-1 reverse transcriptase (RT) which exhibits an IC50 = 84nM in enzyme assays and IC50 = 40nM against HIV-1 replication in cell culture. This nonnucleoside inhibitor acts noncompetitively with respect to nucleoside triphosphates, template and primer suggesting that nevirapine does not bind to the active site of RT. Studies employing an azido analogue of nevirapine as a photoaffinity probe indicated that one molecule of inhibitor is sufficient to inactivate one molecule of heterodimeric enzyme and demonstrated that only the p66 subunit of p66/p51 heterodimeric RT is covalently labeled by this probe. When subjected to trypic mapping, Tyr 181 and Tyr 188 were labeled with probe and consequently these aromatic residues are apparently near or actually within the RT binding site for nevirapine. The extent to which Tyr 181 and Tyr 188 participate/contribute to nevirapine binding was determined by making amino acid substitutions at these positions using the corresponding residues from HIV-2 RT which is not sensitive to nevirapine. A change at either position dramatically decreased the enzymes' sensitivity to nevirapine, as well as to TIBO derivative and Merck L-693,593, indicating that both Tyr 181 and 188 are crucial for inhibitor-enzyme interaction. Cell culture selection in the continued presence of nevirapine results in the appearance of resistant HIV-1, Tyr 181 to Cys, raising the concern that combination drug therapy will be required in the clinic.
 ...
PMID:Nonnucleoside inhibitors of HIV-1 reverse transcriptase: nevirapine as a prototype drug. 137 91

Human immunodeficiency virus type 1 (HIV-1) was isolated from five patients with late-stage disease treated with zidovudine (ZDV) for more than 1 year. Peripheral blood mononuclear cells (PBMCs) were used for all virus isolations and to assay for drug resistance. The isolates exhibited a 10- to 100-fold decrease in ZDV susceptibility compared to pretreatment isolates. Multiple clones of a 618 bp segment of the HIV reverse transcriptase gene encompassing codons 60-250 were sequenced for each isolate. The association of alterations at codons Asp67----Asn, Lys70----Arg, Thr215----Phe or Tyr, and Lys219----Gln with ZDV resistance has been previously noted (ref. 5). In this study, the most frequent alterations was Thr215----Tyr although genotypic mixtures of Thr/Tyr and Phe/Tyr were also observed. One isolate with a Tyr215 alteration and unaltered codons at 67, 70, and 219 had high-level ZDV resistance. Alterations at codons 67, 70, and 219 did not appear to increase resistance when seen in combination with Tyr215. Virus isolates obtained from each patient by cultivation with either 0 or 4 microM ZDV were compared and found to have similar alterations at codons 67, 70, 215, and 219, although one instance of apparent in vitro selection for Tyr215 over Phe215 was observed. Assays using PBMCs for virus propagation will permit susceptibility testing of HIV isolates from most patients on antiretroviral drugs to investigate the clinical significance of drug resistance.
 ...
PMID:Characterization of HIV isolates arising after prolonged zidovudine therapy. 138 38

More than 40 peptides associated with tachyplesin and polyphemusin, which are highly abundant in hemocyte debris of the horseshoe crabs Tachypleus tridentatus and Limulus polyphemus, were synthesized. Among these peptides, we found that a novel compound, which was called T22 ([Tyr-5,12, Lys-7]polyphemusin II), strongly inhibited the human immunodeficiency virus type 1 (HIV-1)-induced cytopathic effect and viral antigen expression. Its 50% effective concentration was 0.008 micrograms/ml, while its 50% cytotoxic concentration was 54 micrograms/ml. The anti-HIV activity of T22 was observed with several strains of HIV-1, including zidovudine-resistant strains, and with HIV-2 within the concentration range of 0.006 to 0.071 microgram/ml. T22 efficiently inhibited giant cell formation on the cocultivation of MOLT-4/HIV and MOLT-4 cells but modestly inhibited direct HIV binding. T22 did not inhibit reverse transcriptase activity. A time-of-addition study, which involved monitoring of the appearance of proviral DNA by using the polymerase chain reaction technique, found that T22 exerted its effect on a process, most probably virus-cell fusion or uncoating, immediately after virus adsorption.
 ...
PMID:Anti-human immunodeficiency virus activity of a novel synthetic peptide, T22 ([Tyr-5,12, Lys-7]polyphemusin II): a possible inhibitor of virus-cell fusion. 138 24

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.
 ...
PMID:Sulfation of the human immunodeficiency virus envelope glycoprotein. 143

Peptide T (H-Ala-Ser-Thr-Thr-Thr-Asn-Tyr-Thr-OH), a fragment of HIV gp120, has been reported to inhibit binding of the virus to the CD4 receptor. The peptide assumes a beta-turn secondary structure, and stabilization of the conformation may increase the biological activity. We synthesized the octapeptide and its C-terminal pentapeptide fragment, unmodified and glycosylated, when monosaccharides were walked through the molecules. Incorporation of the sugar into the longer peptide resulted in the stabilization of the type I (III) beta-turn, as indicated by circular dichroism measurements. While N-terminal glycosylation of the shorter peptide also stabilized the type I (III) beta-turn, the circular dichroism spectra revealed slightly different type II beta-turn structures when the carbohydrate moiety was incorporated into mid-chain or C-terminal positions. Modification of biologically active reverse-turn structures by glycosylation offers a viable alternative to the peptide mimetics approach in drug design.
 ...
PMID:Chemical glycosylation of peptide T at natural and artificial glycosylation sites stabilizes or rearranges the dominant reverse turn structure. 157 31

In this present report we compare the humoral immune response induced by immunization with an HIV-1 gp160 peptide corresponding to amino acid sequence 503-535 complexed with different adjuvants. Specifically, the antipeptide, anti-HIV-1 gp160 and neutralizing antibody responses were measured in groups of mice and baboons that received peptide 503-535 conjugated to a carrier protein in either saline, alum, or stearyl tyrosine. The highest antibody responses were induced when mice and baboons were immunized with peptide adsorbed on stearyl tyrosine. These data indicate that stearyl tyrosine represents a potent candidate as a nontoxic adjuvant not only for subunit viral vaccines, but also for HIV peptides.
 ...
PMID:Adjuvanticity of stearyl tyrosine on the antibody response to peptide 503-535 from HIV gp160. 161 85

A critical step in the replicative cycle of the human immunodeficiency virus HIV-1 involves the proteolytic processing of the polyprotein products Prgag and Prgag-pol that are encoded by the gag and pol genes in the viral genome. Inhibitors of this processing step have the potential to be important therapeutic agents in the management of acquired immunodeficiency syndrome. Current assays for inhibitors of HIV-1 protease are slow, cumbersome, or susceptible to interference by test compounds. An approach to the generation of a rapid, sensitive assay for HIV-1 protease inhibitors that is devoid of interference problems is to use a capture system which allows for isolation of the products from the reaction mixture prior to signal quantitation. In this paper, we describe a novel method for the detection of HIV-1 protease inhibitors utilizing the concept of particle concentration fluorescence. Our approach involves the use of the HIV-1 protease peptide substrate Ser-Gln-Asn-Tyr-Pro-Ile-Val which has been modified to contain a biotin moiety on one side and a fluorescein reporter molecule on the other side of the scissile Tyr-Pro bond. This substrate is efficiently cleaved by the HIV-1 protease and the reaction can be readily quantitated. Known inhibitors of the protease were readily detected using this new assay. In addition, this approach is compatible with existing instrumentation in use for broad screening and is highly sensitive, accurate, and reproducible.
 ...
PMID:Design and implementation of a particle concentration fluorescence method for the detection of HIV-1 protease inhibitors. 162 70


1 2 3 4 5 6 7 8 9 10 Next >>