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)

Toward gene therapy for the treatment of human immunodeficiency virus type 1 (HIV-1) infections in AIDS, Moloney murine leukemia virus-derived retroviral vectors were engineered to allow constitutive and tat-inducible expression of an HIV-1 5' leader sequence-specific ribozyme (Rz1). These vectors were used to infect the human CD4+ lymphocyte-derived MT4 cell line. The stable MT4 transformants expressing an HIV-1 RNA-specific ribozyme, under the control of the herpes simplex virus thymidine kinase (tk) promoter, were found to be somewhat resistant to HIV-1 infection as virus production was delayed. In cells allowing ribozyme expression under control of the simian virus 40 or cytomegalovirus promoter, the rate of HIV-1 multiplication was slightly decreased, and virus production was delayed by about 14 days. The highest level of resistance to HIV-1 infection was observed in MT4 cells transformed with a vector containing a fusion tk-TAR (trans activation-responsive) promoter to allow ribozyme expression in a constitutive and tat-inducible manner; no HIV-1 production was observed 22 days after infection of these cells. These results indicate that retroviral vectors expressing HIV-1 RNA-specific ribozymes can be used to confer resistance to HIV-1 infection.
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PMID:Resistance to human immunodeficiency virus type 1 (HIV-1) infection in human CD4+ lymphocyte-derived cell lines conferred by using retroviral vectors expressing an HIV-1 RNA-specific ribozyme. 189 2

We describe a novel nucleoside analog, 2'-deoxy-3'-thiacytidine (BCH-189), in which the 3' carbon of the ribose ring of 2'-deoxycytidine has been replaced by a sulfur atom. In MT-4 T cells, this compound had significant time- and dose-dependent antiviral activity against five different strains of human immunodeficiency virus type 1 (HIV-1) (mean 50% inhibitory dose, 0.73 microM); known 3'-azido-3'-deoxythymidine (AZT)-resistant HIV-1 variants did not exhibit cross-resistance to it. BCH-189 also suppressed HIV-1 replication in the U937 monocytoid cell line as well as in primary cultures of human peripheral blood mononuclear cells; in these latter systems, suppression was fuller and longer lasting than that induced by AZT. Moreover, BCH-189 was less toxic than AZT in cell culture. BCH-189 may be a promising drug for the treatment of HIV-1-associated disease.
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PMID:Anti-human immunodeficiency virus type 1 activity and in vitro toxicity of 2'-deoxy-3'-thiacytidine (BCH-189), a novel heterocyclic nucleoside analog. 192 98

A novel 6-substituted acyclouridine derivative, 5-ethyl-1-ethoxymethyl-6-(phenylthio)uracil (E-EPU), has recently proved to be a highly potent and selective inhibitor of human immunodeficiency virus type 1 (HIV-1) in vitro. Combinations of 3'-azido-2',3'-dideoxythymidine (AZT) and E-EPU synergistically inhibit the replication of HIV-1 in MT-4 cells, whereas the cytotoxic effects of AZT and E-EPU on mock-infected MT-4 cells are not enhanced by the drug combination. Synergistic inhibition of HIV-1 replication has also been observed in peripheral blood lymphocytes. These results indicate that the combination of AZT and E-EPU should be further pursued in the treatment of AIDS.
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PMID:Synergistic inhibition of human immunodeficiency virus type 1 replication by 5-ethyl-1-ethoxymethyl-6-(phenylthio)uracil (E-EPU) and azidothymidine in vitro. 192 4

The anti-HIV effects of mannopyranan sulfate (1) were investigated by using MT-4 cells, namely, an HTLV-I-carrying CD-4 positive cell-line, in vitro. Stereoregular (1----6)-alpha-D-mannopyranan, which had been synthesized by ring-opening polymerization of a 1,6-anhydromannose derivative, was sulfated with piperidine-N-sulfonic acid to provide 1. N.m.r. analysis of 1 indicated that the reactivity of hydroxyl groups was in the order, 3-OH greater than 2-OH much greater than 4-OH. Mannopyranan sulfate having degree of substitution (d.s.) of 1.19-1.83 effectively inhibited HIV-induced cytopathic effects at a concentration of greater than 3.3 micrograms/mL. The anticoagulant activity and the adsorption on concanavalin A of 1 indicated the possibility of selective binding of 1 having d.s. of 1.19-1.83 to HIV-protein.
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PMID:A strong inhibition of HIV-induced cytopathic effects by synthetic (1----6)-alpha-D-mannopyranan sulfate. 195 28

In the first paper of this series a new structure with anti-HIV-1 activity was disclosed and analogues were synthesized to explore the structure-activity relationship of changes in the substituent (R) attached at the N-6 position of 9. This study describes the syntheses and anti-HIV-1 testing of analogues with variations of the five-membered urea ring of the 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk] [1,4]benzodiazepin-2(1H)-one (TIBO) structures. Although many different rings were synthesized to replace the cyclic urea of TIBO, most were found to be inactive in inhibiting the replication of the HIV-1 virus in MT-4 cells. The exceptions were replacement of the urea oxygen with sulfur or selenium to give the corresponding thio- or selenoureas. These were found to be more active than the oxygen counterparts. A small series of analogues was synthesized and tested which allowed direct comparison of urea and thiourea derivatives. Without exception, the latter were always more active than the former. The most active compound of this series (8d) was found to inhibit the HIV-1 virus with an IC50 of 0.012 microM which is comparable to that of AZT.
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PMID:Synthesis and anti-HIV-1 activity of 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-on e (TIBO) derivatives. 2. 195 37

Cells were infected with HIV-1 and tested for C activation using a flow cytometric assay for bound C3 fragments. HIV-infected H9 cells bound increased levels of C3 using normal human serum as a C source only after cells were first incubated with serum containing anti-HIV antibody. Uninfected H9 cells or infected cells incubated with HIV-antibody negative sera did not bind C3. Although C3 bound quickly and was maximal within 10 min, modulation of bound C3 was slow with about 50% loss after 4 h. C3 binding required specific anti-HIV antibody, was blocked by EGTA, and did not occur in C2-deficient serum suggesting that binding was via the classical pathway. The HTLV-1-infected MT-4 cell line also bound high levels of C3 after coinfection with HIV. C3 binding in HIV-infected MT4 cells was also mediated via the classical pathway because it was not observed in Mg-EGTA chelated or C2-deficient sera. However, this classical pathway activation appeared to be antibody independent because it was also detected in HIV-antibody negative serum and a-gamma-globulinemic serum. This indicates that coinfection with HTLV-1 and HIV-1 can produce novel C activating conditions. No cytotoxic effect of human C for antibody-treated HIV-infected cells was observed in a chromium release assay. However, rabbit C was cytotoxic for HIV-infected cells in the absence of anti-HIV antibodies. Our results suggest that C can be activated in vivo by infected cells via specific anti-HIV antibody. The resultant C3 deposition on infected cells could have profound effects on interaction with CR-bearing cells.
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PMID:Activation of complement on the surface of cells infected by human immunodeficiency virus. 196 81

Experiments were designed to determine whether HIV-1 and herpes simplex virus type 2 (HSV-2) coinfection leads to simultaneous replication of both viruses in the same human CD4+ cell (MT-4 cell line) and the possible effects of coinfection on infectious virus production. Results from transmission electron microscopy analysis revealed replication of typical HSV-2 nucleocapsids in the nucleus and budding of HIV-1 particles through the plasma membrane and through intracytoplasmic vacuoles containing enveloped HSV-2 particles in the same coinfected cell. Coinfection of HIV-1 persistently infected H9IIIB or promonocytic U1 cells with HSV-2 did not alter total production of infectious HSV-2 or the percentage of HSV-2 infectious centers compared with control H9 and U937 cells infected with HSV-2 alone. However, in coinfected promonocytic U1 cells HSV-2 induced infectious HIV-1 production measured by syncytial plaque assay. In summary, both HIV-1 and HSV-2 can coinfect and simultaneously replicate in the same human CD4+ cell. Interactions between HIV-1 and HSV-2 appear to be unidirectional, resulting in accelerated replication of HIV-1 as reported by Albrecht et al. (J Virol 1989;63:1861-1868), but not HSV-2 as shown by us.
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PMID:Human immunodeficiency virus type 1 (HIV-1) and herpes simplex virus type 2 (HSV-2) can coinfect and simultaneously replicate in the same human CD4+ cell: effect of coinfection on infectious HSV-2 and HIV-1 replication. 197 88

An isolate of the human herpesvirus-6 (HHV-6SF) recovered from the saliva of an HIV-infected individual differs in its cellular host range and certain genomic properties from other HHV-6 strains described. HHV-6SF replicates in adult peripheral blood mononuclear cells (PMC) substantially better than in fetal cord blood PMC and can be grown only in the MT-4 established T cell line. It preferentially infects CD4+ lymphocytes but can replicate in CD8+ cells and peripheral blood macrophages. It also infects neuroblastoma cells and cell lines derived from the gastrointestinal tract. These latter results suggest that this herpesvirus could play a role in disorders affecting these tissues. Finally, the restriction enzyme pattern of HHV-6SF differs from that of other HHV-6 strains. The identification of this distinct HHV-6 strain could indicate an unusual biologic variation among viral isolates thus far not observed with other herpesviruses.
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PMID:Characterization of a new strain of HHV-6 (HHV-6SF) recovered from the saliva of an HIV-infected individual. 197 42

Elevations in the levels of unsaturated fatty acids (FAs) in membrane lipids lead to an increase in cell membrane fluidity and may also be involved in cell fusion and death through the loss of normal membrane function and integrity. Since the infection of susceptible cells with HIV leads to cell fusion and subsequent loss of viability, the present study was undertaken to see whether HIV infection can alter the relative content of unsaturated FAs in the host cell membrane and to determine whether this change correlates with cell death. Peripheral lymphocytes (PBLs) of a healthy donor and two CD4+ cell lines were chosen: MT-4, which is killed following HIV infection, with significant cell death being observed 5 days postinfection, and H9 which is not killed. Measurements of FA content of the two cell lines and PBLs, either before or at 6, 24, and 48 h after infection, showed a significant rise in the concentration of unsaturated FAs followed by a drop in the concentration of saturated FAs in the MT-4 cell line. With regard to the H9 cell line similar results were obtained at 6 h from infection. However, at 24 and 48 h the concentrations of saturated FAs returned to preinfection levels while the concentrations of unsaturated FAs dropped to levels even lower than those obtained at zero time. No significant changes in FA composition were found with PBLs.
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PMID:The effect of HIV-1 infection on the lipid fatty acid content in the membrane of cultured lymphocytes. 197 25

The delivery of the anti-HIV agent 3'-azido-3'-deoxythymidine (AZT), in its 5'-monophosphate form, (in) to human T-lymphocyte MT-4 cells in vitro through covalent coupling to neoglycoproteins was investigated. In vivo application of this drug targeting concept may lead to increased efficacy and/or diminished side effects caused by AZT during the treatment of AIDS and ARC patients. The rationale for the design of the neoglycoprotein carriers is based on the existence of sugar recognizing lectins on T-lymphocytes. Using a phenyl-linkage between sugar and Human Serum Albumin (HSA), various mannose-, fucose-, galactose-and glucose-containing neoglycoproteins were synthesized. The intrinsic anti-HIV activity of these neoglycoproteins was tested in vitro in HIV-1 infected MT-4 cells. Only the derivative having 40 moles mannose per mole protein (Man40HSA) shows pronounced anti-HIV-1 activity itself. This effect may be caused by interference of the Man40HSA with the gp120-CD4 mediated virus/MT-4 cell interaction. After conjugation with AZTMP, the mannose- as well as the fucose- and galactose-containing conjugates exhibited a pronounced activity. Conjugates of glucose-HSA and HSA displayed much less activity in spite of the fact that drug loading was considerably higher, compared with the galactose, mannose and fucose derivatives. In the series of mannose-neoglycoproteins, the Man22HSA-AZTMP conjugate was shown to be more than 30 times as active against HIV-1 compared to HSA-AZTMP. Selectivity indices of Man7 and Man22HSA-AZTMP were exceeding the AZT and AZTMP indices, indicating that these conjugates possess a more selective action. Stability experiments indicate that the potent action of the galactose-, mannose- and fucose-HSA-AZTMP conjugates is not due to a complete extracellular hydrolysis of the covalent drug-protein bond. Since Man22HSA has no intrinsic activity in the concentration range used, the antiviral effect is unlikely to be explained by synergism of the neoglycoprotein by a component of the cell membrane and subsequent internalization and release of the drug from the conjugate may play a role.
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PMID:Targeting of antiviral drugs to T4-lymphocytes. Anti-HIV activity of neoglycoprotein-AZTMP conjugates in vitro. 197 34


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