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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human choriocarcinoma cells of the JAR line, with no demonstrable surface CD4 receptor were infected with human immunodeficiency virus type 1 (HIV-1), strain RF. Primer-directed enzymatic DNA amplification (polymerase chain reaction, PCR) detected the presence of viral DNA when the cultures were investigated at day 5 post-infection (p.i.). The absence of cytopathic changes attributable to virus replication suggested silent infection of these malignant trophoblastic cells. Neither reverse transcriptase (RT) activity nor HIV-specific antigens were found in the culture nutrient medium during JAR cell propagation. However, when the HIV-carrier JAR cells were continuously cultured and the cocultivation was initiated with CEM-SS lymphoblastoid cells after two subsequent passages, rescue of infectious virus was observed.
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PMID:In vitro productive infection of human malignant trophoblastic cell line JAR with human immunodeficiency virus type 1 (HIV-1). 168 80

This study describes the derivation of a series of mutants from the human leukemic cell line CEM using the frame shift mutagen Ethyl-methanesulfonate followed by negative selection with multiple treatments of OKT4A + C, and sorting into CD4-, CD4-dull, and CD4-intermediate mutants. These mutants express reduced CD4 levels ranging from 0 to 60% of the parental line. The mutants were analyzed by staining with a battery of CD4-specific mAb, by assessing their ability to bind soluble gp120, and by their ability to form syncytia after infection with cell-free HIV I virus and a gp160-vaccinia vector. Two groups of particularly interesting mutants were identified: (1) CD4-dull mutants expressing only 5 to 10% of the wild type surface CD4 density, which nevertheless were infectable by HIV I and produced as many syncytia and reverse transcriptase activity as the parental line after infection with gp160-vaccinia or cell free HIV I. (2) CD4-intermediate mutants (30 to 60% of parental CD4 level), which express CD4-epitopes required for interaction with the HIV I envelope protein, yet are markedly deficient in their ability to form syncytia after gp160-vaccinia or HIV I infection. Two of these mutants did form syncytia after transient reconstitution with a wild type CD4 containing vaccinia vector. Inasmuch as they were found to bind soluble gp120 with the same avidity as other, functionally normal, CD4-intermediate mutants, these human T cell mutants may have a reduced susceptibility to HIV I infection due to the absence of a "fusogenic component" or to a structural alteration in a region of the CD4 molecule not required for binding of the HIV I envelope, but for the subsequent fusion and entry process.
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PMID:Chemically induced CD4 mutants of a human T cell line. Evidence for dissociation between binding of HIV I envelope and susceptibility to HIV I infection and syncytia formation. 169 Feb 35

We have shown previously that two fractions (PC6 and PC7) extracted from cones of the Japanese white pine Pinus parvifloria Sieb. et Zucc have potent immunopotentiating effects. Here, we show that PC6 and PC7 inhibited HIV-1 replication (greater than 95%), in a dose-dependent manner, in chronically infected CR10/HIV-1 cells and in acute cytolytic HIV-1 infection of CEM cells. Treatment of CEM cells, prior to or after acute infection with HIV-1, reduced subsequent viral production, but the best inhibitory effect was obtained with treatment before and after infection: an 80% inhibition was achieved with as little as 3 micrograms/ml of PC6. Comparable results were also obtained when PC6 was used to inhibit HIV-1 replication in the U937 human histiocytic lymphoma cell line. Both PC6 and PC7 were relatively nontoxic to cells. The anti-HIV-1 effect of PC6 and PC7 we observed in this report, coupled with earlier reports of their immunopotentiating properties suggest their potential as ideal therapeutic agents for the treatment of AIDS.
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PMID:Modification of human immunodeficiency viral replication by pine cone extracts. 169 54

A new class of membrane-active ether lipid (EL) analogs of platelet-activating factor were studied for in vitro anti-HIV-1 activity. Human T-cell (CEM-ss) monolayers or suspension cultures were used to determine effects of structural modifications of Type A phosphorus-containing and Type B nonphosphorus EL analogs on (a) the inhibitory concentration50 (IC50) for HIV-1 syncytial plaque formation and cell growth, and, (b) virus budding at the cell plasma membrane. Results indicate that representative Type A and Type B EL inhibit HIV-1 but not herpes simplex virus type 2 plaque formation when added before or up to 2 days after viral infection. Anti-HIV-1 activity does not involve direct inactivation of virus infectivity. Type A EL (IC50 range = 0.2-1.4 microM) with alkyoxy, alkylthio, or alkyamido substitution at glycerol position 1 and ethoxy or methoxy substitution at position 2, and Type B compounds (IC50 range = 0.33-0.63 microM) with an inverse choline or nitrogen heterocyclic substitution at position 3 have selective activity against HIV-1-infected T-cells. EL treatment of HIV-1-infected cells is associated with subsequent release of reverse transcriptase activity, but infectious virus production is inhibited with time after infection. Electron microscopic examination of HIV-1-infected and EL-treated cells revealed absence of detectable budding virus at the plasma membrane but presence of intracytoplasmic vacuolar virus particles. In summary, these data suggest that EL analogs are a novel class of agents that induce defective intracytoplasmic vacuolar HIV-1 formation in T-cells. Being membrane interactive, EL are ideally suited for combination chemotherapy with DNA-interactive anti-HIV nucleoside analogs.
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PMID:Novel membrane-interactive ether lipid analogs that inhibit infectious HIV-1 production and induce defective virus formation. 169 29

Three analogs of thymidine, D4T [2',3'-didehydro-2',3'-dideoxythymidine; 1-(2,3-dideoxy-beta-D-glyceropent-2-enofuranosyl)thymine], FddT (3'-fluoro-3'-deoxythymidine), and AZT (3'-azido-3'-deoxythymidine), were compared in biological tests designed to assess their potential utility as anti-human immunodeficiency virus (HIV) agents. The in vitro potencies of these compounds against HIV infection in CEM cells were measured, with FddT and AZT being more potent than D4T. The cytotoxicities of D4T, FddT, and AZT for CEM cells were comparable. The triphosphates of these three derivatives inhibited purified HIV reverse transcriptase, and their affinities for this polymerase were found to be 1 or 2 orders of magnitude greater than that for the normal substrate, dTTP. D4T was less toxic than FddT or AZT for cultured human and mouse bone marrow cells (granulocyte-macrophage CFU). The three compounds had similar toxicities for human progenitor erythrocyte burst-forming units. In a 30-day mouse toxicity study, AZT and FddT produced a similar spectrum of hematopoietic toxicities. These toxic effects occurred at much lower doses of FddT than of AZT. At the higher doses of FddT, a significant incidence of lethality occurred. By contrast, D4T was considerably less toxic than both AZT and FddT in this study. The dose-limiting toxicity of D4T in mice was hepatotoxicity. The very different phosphorylation patterns of D4T, its lower toxicity, and its comparable potency relative to FddT and AZT suggest that the potential of D4T as an anti-HIV agent should be further explored.
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PMID:Comparison of in vitro biological properties and mouse toxicities of three thymidine analogs active against human immunodeficiency virus. 169 57

Syncytium formation between HUT-78 cells persistently infected with human immunodeficiency virus type 1 (HIV-1) and uninfected CD4-bearing MOLT-4 or CEM cells results in a rapid destruction of the MOLT-4 or CEM cells. This syncytium formation is due to the interaction between the gp120 glycoprotein expressed by the persistently HIV-1-infected HUT-78 cells and the CD4 receptor present on MOLT-4 or CEM cells. A flow cytometric method has been applied to separate the infected (HUT-78) from the uninfected (MOLT-4, CEM) cell populations. This method is based on a modified DNA staining protocol which clearly shows the differences in DNA content between HUT-78 cells, on the one hand, and MOLT-4 or CEM cells, on the other hand. Using this flow cytometric method we have demonstrated that those compounds (i.e., sulfated polysaccharides, aurintricarboxylic acid) that interact with gp120 (of the HIV-infected cells) or CD4 (of the uninfected cells) suppress syncytium formation and concomitant destruction of the CD4+ cells.
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PMID:Flow cytometric method to monitor the destruction of CD4+ cells following their fusion with HIV-infected cells. 169 39

In an effort to determine the functional activity of anti-HIV-1 human mAb and to define the epitopes against which they are directed, supernatants from 10 EBV-transformed lymphoblastoid cell lines producing mAb to HIV were tested. Five clones producing mAb to gp41 and five producing mAb to p24 were identified. The anti-HIV-1 human mAb were tested in neutralization and cell fusion assays in the form of cell culture supernatants at concentrations ranging from 1.7 to 22.0 micrograms/ml. None of the human mAb were found either to inhibit HIV-1-(IIIB or RF) associated cell fusion or to neutralize HIV-1 (IIIB) infection of AA5 cells. All human mAb were additionally tested in 6 h 51Cr release assays for their ability to direct HIV-1 specific antibody-dependent cellular cytotoxicity (ADCC). For ADCC assays, PBMC were isolated from healthy seronegative donors and used as effector cells. HIV-1 infected (IIIB, RF, and MN) CEM.NKR cells as well as CEM.NKR cells with purified gp120 adsorbed onto their surface served as targets. None of the anti-p24 mAb mediated ADCC. In contrast, three of the anti-gp41 mAb were able to direct a significant level of ADCC against each of the infected targets, but as expected, failed to lyse gp120 adsorbed cells. To define the specific epitopes against which the anti-gp41 mAb were directed, seven small peptides homologous to regions within the extracellular domain of gp41 were synthesized. Using RIA, two of the mAb could be mapped. The most effective ADCC-directing human mAb bound to a peptide comprising amino acids 644-663, whereas the least effective ADCC directing anti-gp41 human mAb bound to a region within the immunodominant portion of gp41 outlined by amino acids 579-604. Together, these results for the first time assign a functional activity to human mAb directed at specific regions within gp41 by demonstrating that areas within this molecule can serve as targets for ADCC.
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PMID:Identification of sites within gp41 that serve as targets for antibody-dependent cellular cytotoxicity by using human monoclonal antibodies. 170 4

Aurintricarboxylic acid (ATA) was fractionated by a combination of dialysis, ultrafiltration, and gel permeation chromatography. The number average and weight average molecular weights of the ATA fractions were determined by the universal calibration method. The sulfonic acid analogue of ATA was prepared and separated in high and low molecular weight fractions. The phosphonic acid analogue of ATA was also synthesized. All of the ATA fractions were tested for prevention of the cytopathic effect of HIV-1 and HIV-2 in MT-4 cell culture as well as against HIV-1 in CEM cell culture. The abilities of the fractions and analogues to inhibit syncytium formation between HIV-1- and HIV-2-infected HUT-78 cells and uninfected MOLT-4 cells were evaluated. In addition, the fractions and analogues were tested for cytotoxicity in mock-infected MT-4 cells, prevention of the binding of the OKT4A monoclonal antibody to the CD4 receptor, inhibition of the binding of anti-gp120 monoclonal antibody to gp120, inhibition of attachment of HIV-1 virions to MT-4 cells, and inhibition of HIV-1 reverse transcriptase. In all of these assays except cytotoxicity, there was a correlation of potency with molecular weight. The higher the molecular weight, the higher the activity. Several of the lower molecular weight fractions of ATA, which bound to gp120 but not to CD4, prevented HIV-1 and HIV-2 cytopathicity. A similar profile was observed for the phosphonic acid analogue of ATA and the lower molecular weight fraction of the sulfonic acid analogue. The results on the ATA fractions indicate that the binding of ATA to gp120 in the absence of CD4 binding is sufficient for anti-HIV activity. The active compounds bind more avidly to gp120 than to CD4. The anti-HIV activity of the ATA fractions is due to inhibition of virus binding due to an interference with the gp120-CD4 interaction.
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PMID:Preparation and anti-HIV activities of aurintricarboxylic acid fractions and analogues: direct correlation of antiviral potency with molecular weight. 170 65

Several compounds corresponding to fragments of the schematic representation of the polymeric structure of aurintricarboxylic acid (ATA) have been prepared and tested for prevention of the cytopathic effect of HIV-1 and HIV-2 in MT-4 cell culture and HIV-1 in CEM cell culture. Both the triphenylcarbinol 3 as well as the triphenylmethane 5 were found to afford protection against the cytopathogenicity of HIV-2 in MT-4 cells and HIV-1 in CEM cells, but they were inactive against HIV-1 in MT-4 cells. Both substances were also found to inhibit syncytium formation when MOLT-4 cells were cocultured with HIV-2-infected HUT-78 cells, but were inactive in this assay against HIV-1-infected cells. When observed, the activity is generally moderate in degree of protection and requires concentrations in the 10(-4) molar range. In contrast to ATA, both of these substances were inactive when tested for prevention of the binding of the OKT4A monoclonal antibody to the CD4 receptor and also for inhibition of HIV-1 reverse transcriptase. These substances therefore appear act by a mechanism that is distinct from that of polymeric ATA. Several active and inactive structural analogues of 3 and 5 were also synthesized. The anti-HIV activity in this series seems to depend on the presence of anionic carboxylate groups, since the methyl esters 4, 6, and 12 were uniformly inactive. The diphenylmethanes 8, 14, 18, and 19 also reproducibly inhibited the cytopathic effect of HIV-1 in CEM cell culture.
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PMID:Synthesis and anti-HIV activities of low molecular weight aurintricarboxylic acid fragments and related compounds. 170 66

Differential susceptibility of four diverse HIV strains to inhibition of infection of CD4+ CEM cells by anti-CD4 monoclonal antibodies was studied. The highly cytopathic HIV-1 246 and NDK strains were able to infect CEM cells and undergo several cycles of replication at saturating doses of LEU3-A, OKT4-A, and 13B8-2 monoclonal antibodies, whereas propagation of reference HIV-1 BRU and weakly cytopathic strain HIV-1 PAS was inhibited. Postadsorption treatment by anti-CD4 antibodies had stronger inhibitory effect than did treatment during the virus adsorption period. In parallel experiments, the same monoclonal antibodies successfully blocked syncytium formation between uninfected MT4 cells and CEM cells infected by all four HIV-1 virus strains tested. To explain these seemingly contradictory data we have postulated that anti-CD4 antibodies efficiently inhibit cell-to-cell but not virus-to-cell infection.
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PMID:Productive infection of CD4+ cells by selected HIV strains is not inhibited by anti-CD4 monoclonal antibodies. 170 55


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