Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alpha-lipoic acid, a naturally occurring disulfide-compound that acts as a cellular coenzyme, inhibits replication of HIV-1 in cultured lymphoid T-cells. Alpha-lipoic acid was added 16 hours after infection of the T-cell lines Jurkat, SupT1 and Molt-4 with HTLV IIIB and HIV-1 Wal (a wild type HIV-1 isolate). We observed a dose dependent inhibition of HIV-1-replication in CPE (Cytopathic effect) formation, reverse transcriptase activity and plaque formation on CD4-transformed HeLa-cells. An over 90% reduction of reverse transcriptase activity could be achieved with 70 micrograms alpha-lipoic acid/ml, a complete reduction of plaque-forming units at concentrations of greater than or equal to 35 micrograms alpha-lipoic acid/ml. An augmentation of the antiviral activity was seen by combination of zidovudine and low dose of alpha-lipoic acid (7 micrograms/ml). Trypan blue staining revealed no toxic effects of alpha-lipoic acids on peripheral blood mono-nuclear cells and T-cell lines even in concentrations of greater than or equal to 70 micrograms/ml. Therefore, we propose the inclusion of alpha-lipoic acid into chemotherapy trials in combination with zidovudine.
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PMID:Alpha-lipoic acid is an effective inhibitor of human immuno-deficiency virus (HIV-1) replication. 172 77

The carcinogen-treated cockerel is a model for studying the early stages of arteriosclerotic plaque development. Carcinogen administration accelerates arteriosclerotic plaque development in cockerels, and transforming elements are present in DNA from advanced human plaques. In this study, we asked whether transforming elements could also be detected at early stages of plaque development in cockerels. NIH3T3 cells were transfected with DNA from plaques isolated from carcinogen-treated cockerels and from the healthy arterial wall underlying the plaques. Approximately 5 x 10(6) cells from each group were injected into nude mice. Tumors appeared in five of five mice in the plaque DNA group; no tumors appeared in mice from the healthy arterial wall group. All five plaque DNA-associated tumors hybridized to a cockerel genomic probe. Eight cockerel-specific bands were identified in EcoRI digests of first-round (primary) tumors. DNA from a primary tumor was tested in a second round of transfection. Five of five mice developed tumors after injection with these secondary transformants. All second-round tumors contained cockerel DNA, and a prominent cockerel-specific band (greater than 28 kb) was seen in EcoRI digests of all second-round tumors. In addition, a 5.2-kb band appeared prominently in one of five second-round tumors. No evidence was found for activation of the oncogenes Ha-ras, Ki-ras, src, or myc in the plaque-associated tumors. Similarly, DNA from plaque-associated tumors did not hybridize to probes for Marek disease virus, herpes simplex virus 1, or reverse transcriptase, suggesting that neither herpesviruses nor retroviruses are involved in the transforming activity of plaque DNA. These results indicate that transforming elements are a general property of arteriosclerotic plaques and are detectable in plaques of young animals.
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PMID:Transforming potential is detectable in arteriosclerotic plaques of young animals. 190 51

A series of synthetic lipids containing a two- or three-carbon backbone substituted with a thio, oxy, or amidoalkyl functionality and either a phosphocholine or quaternary ammonium moiety was evaluated as potential anti-HIV-1 agents. Several analogues were identified as possessing activity with the most promising compound being rac-3-octadecanamido-2-ethoxypropylphosphocholine (8). Compound 8 exhibited an IC50 for the inhibition of plaque formation of 0.16 microM which was 84-fold lower than the IC50 value determined for CEM-SS cell growth inhibition. Initial mechanistic studies have indicated that these compounds, unlike AZT, are not reverse transcriptase (RT) inhibitors, but instead appear to inhibit a late step in HIV replication involving virus assembly and infectious virus production. Since these lipids are acting via a different mechanism, they represent an alternative approach to the chemotherapeutic treatment of AIDS as well as candidates for combination therapy with AZT.
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PMID:In vitro evaluation of phosphocholine and quaternary ammonium containing lipids as novel anti-HIV agents. 201 13

Early events in the infection of the human T-lymphotropic virus type-I (HTLV-I)-positive MT-4 cell line by the acquired immune deficiency syndrome (AIDS) retrovirus HTLV-III were investigated. The virus was adsorbed completely to the cells within 60 min incubation after inoculation of the virus. Then, infected MT-4 cells started to produce the HTLV-III-specific antigens between 12 and 24 hr postinfection. Synthesis of the viral antigens consisting of 120K, 46K, 24K, and 17K polypeptides was suppressed by the treatment of the virus-infected MT-4 cells with cytosine arabinoside (Ara-C) or by the treatment of the virus with anti-HTLV-III-positive sera. The progeny of the virus released from the infected MT-4 cells was titrated by a newly developed plaque-forming assay method and reverse transcriptase activity. The maximum activity of HTLV-III (3 X 10(5) PFU/ml) was observed on Days 4 and 5 p.i. Most of the viral activities in this preparation were ascribed to HTLV-III, and not to HTLV-I. No phenotypic mixing between HTLV-III and HTLV-I was discerned, although MT-4 cells were HTLV-I-producer cell line. Thus, HTLV-III-infected MT-4 cells are thought to be useful in further study of the interaction between host cells and the virus, and appear to be a good viral source for the analysis of the virus.
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PMID:Infection of human T-lymphotropic virus type-I (HTLV-I)-bearing MT-4 cells with HTLV-III (AIDS virus): chronological studies of early events. 241 16

Retroviral propagation crucially depends on reverse transcriptase (RT). We have developed murine models to test the biological effectiveness of the RT inhibitor suramin. The drug was active in our assay system, which includes (i) inhibition of RT activity in the murine T-cell tropic virus SL3-3 and Rauscher murine leukemia virus (MuLV), (ii) inhibition of plaque formation in the XC plaque assay, (iii) inhibition of viral infection of cultured murine T cells, and (iv) inhibition of splenomegaly induced by Rauscher MuLV in BALB/c mice. Suramin decreases viral titers significantly, even if started 36 hr after infection. Viral titers and number of infected cells increased to control levels after removal of the drug. BALB/c mice treated i.v. with 40 mg of suramin per kg twice per week following infection with Rauscher MuLV showed a 35% decrease in splenomegaly. Suramin is an active antiretroviral agent whose effect on retroviral propagation is reversible. We conclude that it acts as a virustatic drug and that long-term administration of suramin will be necessary if it is used for experimental treatment of human retroviral illnesses such as the acquired immune deficiency syndrome.
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PMID:Suppression of retroviral propagation and disease by suramin in murine systems. 241 71

The expression of the type-C retrovirus and the virus-related components in NFS mice were examined during preleukemic and leukemic phases after fractionated whole-body X irradiation. The NFS mice were highly susceptible to induction of thymoma by fractionated X irradiation. The leukemic tissues were negative for infectious type-C virus, as detected by both the XC-plaque test and mink S+ L- focus-inducing assays, but contained a substantially higher level of viral-specific RNA-dependent DNA polymerase activity and a major core protein p30 than the corresponding tissues from unirradiated age-control mice. In the preleukemic phase, the amount of p30-related antigen increased transiently in spleen. The leukemic cell lines established from radiation-induced lymphomas produced particulate entities with a buoyant density of about 1.15 g/ml. These virus-like particles lacked in vitro infectivity to mouse cells and mink lung cells and leukemogenicity in syngeneic mice. The p30-related antigens of these particles were immunologically similar to that of xenotropic virus derived from NZB mouse.
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PMID:Endogenous type-C viral expression during lymphoma development in irradiated NFS mice. 241 71

Human T cell lymphotropic virus type III (HTLV-III)/lymphadenopathy-associated virus is the etiologic agent of the acquired immune deficiency syndrome (AIDS) and AIDS-related complex. The effect of 3'-azido-3'-deoxythymidine (AZT) on the HTLV-III/lymphadenopathy-associated virus infection was quantitatively studied with HTLV type I-carrying MT-4 cells. The AZT compound inhibited HTLV-III-induced cytopathic effect and virus-specific antigen expression in MT-4 cells at concentrations of 5 and 10 microM. In addition, a plaque-forming assay was performed to assess the effect of AZT on virus replication in MT-4 cells freshly infected with HTLV-III and in continuous HTLV-III-producing Molt-4/HTLV-III cells. Results showed that AZT efficiently and effectively inhibited the replication of HTLV-III in infected MT-4 cells. AZT is a strong inhibitor of reverse transcriptase activity of HTLV-III as a triphosphate, to such a degree that even 1.0 pM azido-TTP inhibits 50% of reverse transcriptase activity. However, it did not show any effect in the HTLV-III-producing cell line Molt-4/HTLV-III. Thus, AZT has no effect on virus replication of an already integrated virus. When 5 microM AZT was added to HTLV-III-infected MT-4 within 20 h after infection, a striking suppressive effect was noticed. This concentration was much lower than that which inhibits the growth of MT-4 cells. These results confirm those found in a previous report (H. Mitsuya, K. J. Weinhold, P. S. Furman, H. S. Clair, S. N. Lehrman, R. C. Gallo, D. Bolognesi, D. W. Barry, and S. Broder, Proc. Natl. Acad. Sci. USA 82:7096-7100, 1985) and suggest that AZT might be used as an experimental antiviral agent for AIDS and AIDS-related complex.
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PMID:Inhibition of replication and cytopathic effect of human T cell lymphotropic virus type III/lymphadenopathy-associated virus by 3'-azido-3'-deoxythymidine in vitro. 243 24

The inhibitory effect of all-trans-retinoic acid (RA) on human immunodeficiency virus (HIV) replication upon infection was studied quantitatively using a novel bioassay system with a HTLV-I-carrying human T-cell line, MT-4. The results can be summarized as follows. The appearance of HIV antigen was significantly reduced when the cells were treated with more than 1 microgram/ml of the chemical after infection. When HIV specific plaque assay was performed to titrate the virus from the supernatant of culture treated with 10 micrograms/ml of RA no plaques were observed. When RA was applied directly in the plaque assay, significant decrease of the number of plaques was discerned showing 68, 66, 47 and 16, at doses of 0.1, 1, 5, and 10 micrograms/ml of RA, while 102 plaques were formed in the control dish. The appearance of cytopathic effects of MT-4 cells by HIV was more delayed in RA-treated cultures than in untreated cultures. Concomitant treatment of the cells with 5 micrograms/ml of RA and various concentrations of suramin resulted in the more effective inhibition of HIV replication than suramin alone. RA did not inhibit the reverse transcriptase activity (RT) of HIV directly. These data suggest that RA inhibits HIV replication by inducing an antiviral state in the cells.
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PMID:Effect of retinoic acid on the replication of human immunodeficiency virus in HTLV-I-positive MT-4 cells. 244 Dec 39

Glycyrrhizin sulfate (GLS) was synthesized and investigated for antiviral effect on the human immunodeficiency virus (HIV) in vitro in comparison with the parental anti-HIV compound glycyrrhizin (GL). In MT-4 cells after HIV infection, the virus-induced cytopathic effect and the expression of viral antigens were inhibited by 0.25 mg/ml (0.184 mM) of GLS. Moreover, GLS completely inhibited HIV-induced plaque formation in MT-4 cells at a concentration of 1 mg/ml (736 microM), the 50% inhibitory dose being 0.055 mg/ml (40 microM). GLS was found to be an efficient inhibitor of reverse transcriptase. The effect of GLS was 4 times stronger than that of GL in molar terms.
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PMID:A new anti-human immunodeficiency virus substance, glycyrrhizin sulfate; endowment of glycyrrhizin with reverse transcriptase-inhibitory activity by chemical modification. 244 73

A new reverse transcriptase (RT) inhibitor was extracted and purified from the red alga Schizymenia pacifica. The chromatographic behavior and chemical properties of this sea algal extract (SAE) suggest that it is a sulfated polysaccharide having a molecular weight of approximately 2,000,000. SAE is composed of galactose (73%), sulfonate (20%), and 3,6-anhydrogalactose (0.65%). SAE is a member of the lambda-carrageenan family, based on its infrared spectrum and products of hydrolysis. SAE selectively inhibited human immunodeficiency virus (HIV) RT and replication in vitro. When MT-4 cells were treated with more than 10(4) inhibitory units (IU) of SAE per ml after HIV infection, significant inhibition of viral antigen synthesis was observed. Furthermore, more than 90% of cells were viable in the cultures exposed to 4 X 10(4) to 8 X 10(4) IU of SAE per ml, while almost all the MT-4 cells in the control culture had died by 10 days after HIV infection. The inhibitory effect of SAE on HIV replication was confirmed by plaque reduction assays. The 50% inhibitory dose of SAE was 9.5 x 10(3) IU/ml. Chondroitin sulfate A, dermatan sulfate, heparan sulfate, keratan polysulfate, and heparin also inhibited the RT of avian myeloblastosis virus. SAE immediately inhibited RT activity when added to an assay mixture after the start of the reaction.
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PMID:Purification and characterization of an avian myeloblastosis and human immunodeficiency virus reverse transcriptase inhibitor, sulfated polysaccharides extracted from sea algae. 244 20


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