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)

At concentrations of 7 times 10(-6) to 7 times 10(-5) M, derivatives consisting of the polycylic ring structures fluoranthene, fluorenone, fluorene, anthraquinone, xanthenone, and dibenzofuran with appropriate amine side chains inhibited by over 90% the purified RNA-directed DNA polymerase of avian myeloblastosis virus acting on poly(deoxyadenylate-deoxythymidylate) [poly(dA-dT)]. Of these, only the fluoranthene derivatives were strong inhibitors of the viral DNA polymerase directed by polyadenylate-oligodeoxythymidylate [poly(A)-(dT)12-18]. Low levels of fluoranthene derivatives (1 times 10(-5) M) also strongly inhibited polymerase with polyinosinate-oligodeoxycytidylate [poly(I)-(dC)12-18], activated calf thymus DNA, and viral 70S RNA as templates, but not with polycytidylate-oligodeoxyguanylate as template. A comparison of the activity of 11 fluoranthene derivatives with different side chains showed that the structure of the amine side chain influenced both the extent of antipolymerase activity with a given template and the relative inhibition with different synthetic DNA and RNA templates. The naturally occurring polyamines, spermine, spermidine, and putrescine, did not inhibit the activity of the viral DNA polymerase. Studies on the mechanism of action indicated that the synthetic derivatives inhibited polymerase activity by binding to the template and not to the enzyme: 1) inhibition by fluoranthene derivatives was overcome by the addition of excess template including poly(dA-dT), poly(A)-(dT)12-18, poly(I)-(dC)12-18, viral 70S RNA, and activated calf thymus DNA; 2) the degree of inhibition by fluoranthene derivatives was unaffected by the addition of the creased viral DNA polymerase; 3) with the same template, Escherichia coli DNA-directed RNA polymerase and the viral RNA-directed DNA polymerase were inhibited to about the same extent; and 4) the derivatives formed a complex with DNA, poly(I), and poly(A) that was stable to exclusion chromatography on Sephadex G-100. Several derivatives also had biologic activity, since they blocked the ability of the murine sarcoma virus to transform cells.
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PMID:Inhibition of purified DNA polymerase of RNA tumor viruses by fluoranthene derivatives and analogues of tilorone hydrochloride. 5 Oct 87

Short- and long-term co-cultures of 49 cases of human osteosarcoma cells with bone marrow or peripheral blood cells of patients with different types of leukemia were studied. Morphological changes were observed in 7 of 13 long-term co-cultures resembling those induced by RNA tumor viruses. The changes were accompanied by appearance of cytoplasmic antigen as shown by fixed immunofluorescence test with sera from patients with osteosarcoma, leukemia, and of some apparently normal blood donors. Absorption with Forssman-like substances, whole human embryo cells or osteosarcoma cells demonstrated the reaction to be due to tumor antigen(s) in co-culture cells showing morphological changes. Electron microscopy showed a few type C virus particles in one co-culture. Cell-free filtrates of fluid from the transformed co-cultures induced morphological changes in 1 of 4 human embryo cultures. Uninoculated embryo cultures or those inoculated with filtrates from parental sarcoma or leukemia cultures showed no morphological changes. Human embryo cell cultures treated with fluid from parental leukemic bone marrow but not from parental sarcoma cultures showed appearance of cytoplasmic antigen by immunofluorescence test with sera of osteosarcoma and leukemia patients and of some apparently normal blood donors. Transformed human co-cultures showed the cytoplasmic antigen with 28 of 48 sera of osteosarcoma and leukemia patients tested, after absorption with Forssman-like material, human embryo, and mycoplasma suspensions. Fourteen of 49 sera of normal donors were also positive with the transformed co-cultures. Similar results were obtained in an earlier series of experiments with human embryonic cultures transformed by fluid from different osteosarcoma-leukemia co-cultures when examined by fixed immunofluorescence tests with sera of patients with osteosarcoma and leukemia. In 2 whole human embryo cell cultures showing morphological changes high molecular weight RNA was found, similar to that of RNA animal tumor viruses and in one of the cultures transient reverse transcriptase was detected.
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PMID:Virus retrieval studies in human neoplasia. 5 29

We isolated a type-C RNA virus from the Japanese field mouse, Mus musculus molossinus. M. musculus musculus and M. musculus molossinus are two different subspecies of Mus and thus only distantly related. The virus grew only on cells foreign to the host, was xenotropic, and readily rescued the murine sarcoma (MuSV) genome from a normal rat kidney cell line transformed nonproductively by the Harvey strain of MuSV. The virus banded at a density of 1.16 g/ml and contained an RNA-dependent DNA polymerase.
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PMID:Isolation of an endogenous C-type RNA virus from Mus musculus molossinus. 5 16

We have studied the effect of protein phosphokinase (EC 2.7.1.37; ATP:protein phosphotransferase) and phosphoprotein phosphatase (EC 3.1.3.16; phosphoprotein phosphohydrolase) on reverse transcriptase (RNA-dependent DNA nucleotidyltransferase) activity of Rous sarcoma virus. Protein kinase from Rous sarcoma virus-transformed chick embryo fibroblasts was purified by DEAE-cellulose chromatography, Sephadex gel filtration, and isoelectric focusing. Purified reverse transcriptase from Rouse sarcoma virus was preincubated with protein kinase and ATP under conditions allowing incorporation of phosphate into substrate protein. After the preincubation, reverse transcriptase activity was assayed in the presence of poly(rA).oligo(dT) as template. A 2- to 5-fold increase of reverse transcriptase activity was found after the preincubation of reverse transcriptase with protein kinase and ATP. Incubation of reverse transcriptase with heat-treated, inactive protein kinase and ATP had no effect on transcriptase activity. When the transcriptase preparation was incubated with protein kinase and [gamma-32P]ATP and subsequently purified by chromatography on phosphocellulose and Sephadex gel filtration, significant amounts of 32P-labeled proteins were found in the fractions exhibiting reverse transcriptase activity, suggesting 32P incorporation into transcriptase or transcriptase-associated proteins. A 20-60% decrease of reverse transcriptase activity was observed after incubation of reverse transcriptase with phosphatase. The results suggest that phosphorylative modification of reverse transcriptase may be critical in the regulation of reverse transcriptase-catalyzed DNA synthesis.
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PMID:Protein kinase and its regulatory effect on reverse transcriptase activity of Rous sarcoma virus. 5 72

Three temperature-sensitive mutants of the Rauscher strain of murine leukemia virus are defective in early post-penetration functions required both for leukemia virus infection and for initiation of transformation of cells by their pseudotypes of murine sarcoma virus. In the present study, the reverse transcriptase of one of these mutants (ts 29) is shown to be thermolabile compared with the enzymes of the wild-type virus and several other temperature-sensitive mutants. These findings provide evidence that the reverse transcriptase is required both for leukemia virus infection and for initition of transformation by the replication-defective murine sarcoma virus genome.
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PMID:Thermolabile reverse transcriptase of a mammalian leukemia virus mutant temperature sensitive in its replication and sarcoma virus helper functions. 5 94

A cat kidney cell line, CRFK-F2, was successfully inoculated in suspension and in monolayer culture with a purified mouse mammary tumor virus derived from RIII milk. The virus produced by the infected cells was identified by immunogluorescence, electron microscopy, and RNA-directed DNA polymerase assays; it was a B-type virion that did not cross-react with mouse or feline leukemia-sarcoma viruses, had spikes on its envelope, and had a RNA-directed DNA polymerase reaction that was typical of mouse mammary tumor virus. The producing cells were identified as cat cells by chromosome number, cytotoxic assays, and isoenzyme migratory patterns. A standardized method for the in vitro inoculation of cat cells is described that presently permits highly reproducible results. For the first time, the mouse mammary tumor virus is seen replicating in cells from another species, thus offering an opportunity to study the kinetics of infection of that virus.
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PMID:Experimental infection of a cat kidney cell line with the mouse mammary tumor virus. 5 5

Mouse cells transformed by murine sarcoma virus were made resistant to 8-azaguanine. Resistant cells and cell clones isolated from them were deficient in hypoxanthine-guanine phosphoribosyl transferase (HGPRT) activity. They did not grow in HATG medium, did not incorporate labeled hypoxanthine, and had negligible HGPRT activity. The resistance was genetically stable. The resistant cells were hyperdiploid and contained telocentric chromosomes only. The resistant cells as well as the progenitor cells were slightly tumorigenic in mice, the plating efficiency in soft agar was very low. The parental cells and aza-G resistant cells produced C-type viral particles having RNA-dependent DNA polymerase activity. The resistance to aza-G did not influenced the expression of murine sarcoma virus genome in cells. The resistant cells are suitable for preparation of cell hybrids.
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PMID:Mouse MSV transformed cells resistant to 8-azaguanine. 5 81

Short-term cultures of bovine leukemic lymphocytes release virus particles with biochemical properties of RNA oncogenic viruses. These particles, tentatively called bovine leukemia virus (BLV), have a high molecular weight RNA-reverse transcriptase complex and a density of 1.155 g/ml in sucrose solutions. Molecular hybridizations between BLV/[3H]cDNA and several viral RNAs show that BLV is not related to Mason-Pfizer monkey virus, simian sarcoma associated virus, feline leukemia virus, or avian myeloblastosis virus. These results were confirmed by hybridization between BLV 70S RNA and [3H]cDNA synthesized in the various viruses tested. The high preference of BLV reverse transciptase for Mg++ as the divalent cation suggests that BLV might be an atypical mammalian leukemogenic "type C" virus. DNA-DNA hybridization studies using BLV [3H]cDNA as a probe strongly suggest that the DNA of bovine leukemic cells contains viral sequences that cannot be detected in normal bovine DNA.
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PMID:Bovine leukemia virus: an exogenous RNA oncogenic virus. 5 16

Cocultivation of cells derived from embryos of golden pheasants or Amherst pheasants with chicken embryo cells infected with Bryan strain of Rous sarcoma virus resulted in the detection of viruses which appear to be endogenous in these pheasant cells. The pheasant viruses (PV) were similar to avian leukosis-sarcoma viruses (ALSV) in their gross morphology, in the size of their RNA, in the presence of a virion-associated RNA-dependent DNA polymerase (DNA nucleotidyltransferase; deoxynucleoside triphosphate: DNA deoxynucleotidyltransferase; EC 2.7.7.7), and in their growth characteristics. PV also serves as a helper for the glycoprotein-defective Rous sarcoma virus. However, PV was shown to be different from both ALSV and reticuloendotheliosis virus in the following properties: (i) PV does not have ALSV group specific antigens; (ii) the protein composition of PV is different from those of the other two groups of viruses; (iii) PV fails to complement the defective polymerase of alpha type Rous sarcoma virus; and (iv) PV RNA shows no detectable homology with nucleic acids of the other two groups of viruses. Thus, PV appears to be a new class of RNA viruses which contain RNA-dependent DNA polymerase.
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PMID:Pheasant virus: new class of ribodeoxyvirus. 5 21

Type C viruses were isolated from embryo cultures of two different rat strains, Sprague-Dawley and Fischer. Both viruses (termed rat leukemia virus, RaLV) were released spontaneously from rat embryo cells, have a density of 1.14 to 1.15 g/cm(3) based on equilibrium sedimentation in sucrose gradients, contain 60-70S RNA, RNA-directed DNA polymerase, and rat type C virus-specific 30,000 molecular-weight-protein determinants. Molecular hybridization studies using the Sprague-Dawley RaLV 60-70S RNA show that the virus-specific nucleotide sequences are present in the DNA of rat embryos. Both Sprague-Dawley and Fischer RaLV can rescue the murine sarcoma virus genome from Kirsten murine sarcoma virus-transformed nonproducer cells and are neutralized by antisera to the RPL strain of RaLV. In contrast to previous RaLV's, these viruses propagate in their own cells of origin as well as in cells of heterologous rat strains.
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PMID:Spontaneous release of endogenous ecotropic type C virus from rat embryo cultures. 5 77


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