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)

The properties of the virus synthesized by each of three morphologically different cell lines originating from DBA/2J fetal liver cells transformed by the anemic strain of Friend leukemia virus in vitro were analyzed. The cells of line G-1 are malignant in syngeneic DBA/2 mice, grow in suspension, and are erythroid in origin. Cells of lines G-2 and G-3 are adherent, are epithelial in appearance, and produce no tumors in DBA/2J mice. Higher reverse transcriptase activity was detected in the culture fluid of lines G-2 and G-3, although virus from G-1 cells was more leukemogenic. Differences were also found in the virion density and size of the viral genome. RNA from the virions produced by G-2 and G-3 cells sedimented at 75 S in a sucrose gradient; virion RNA from G-1 cells sedmiented at 60 S. However, when subjected to polyacrylamide gel electrophoresis, all three virus strains showed identical RNA subunits with an estimated molecular weight of 2.6 X 10(6). Analysis of virion proteins by slab gel electrophoresis showed differences in envelope protein (gp71) components but not in the major core protein (p30). The properties of these viruses are stable and remain unchanged after passage in 3T3 cells.
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PMID:Variations in properties of virus released from morphologically different cell lines transformed in vitro by Friend leukemia virus. 616 May 80

The biological properties of the virus synthesized by 18 clones of a line of mouse bone-marrow hematopoietic cells transformed in vitro by the polycythemic strain of Friend leukemia virus (FLV-P) were compared. In vitro assays were performed to determine whether the virus released into the culture fluids was ecotropic or xenotropic, and in vivo assays were carried out to determine spleen focus formation and leukemogenicity in susceptible DBA/2J and BALB/c mice. A number of clones released virus which reproduced the entire range of effects typical of the FLY-P complex. However, in other clones, there appeared to be no correlation between the assays for leukemogenicity and the assays for either ecotropic virus, reverse transcriptase activity, or virus antigens. Xenotropic virus was not detected in any of the cultures. These results suggest that the FLV-P complex contains a heterogeneous population of viruses, but the possibility that the differences observed may be due to the inability of FLV-P to be expressed fully in some clones cannot be excluded.
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PMID:Lack of correlation between in vivo and in vitro assays for the detection of virus released from clones of Friend erythroleukemia cells. 616 81

The action of 12-O-tetradecanoylphorbol-13-acetate (TPA) on several retrovirus-related functions was investigated in four virus-host cell systems. The following effects were recorded: (i) in STU-mice, infected with the Friend virus complex (Friend) murine leukaemia virus/Friend spleen focus forming virus) and treated with TPA (50 ng/g) for one week prior to infection, the number of spleen foci increased 5-fold over the control. (ii) Addition of TPA (0.04 to 40 ng/ml) to virus-producing cell systems resulted in a 2-fold increase of extracellular reverse transcriptase activity. The maximum response was observed in Friend leukemia virus-producing mouse cells at 0.1 to 0.4 ng TPA/ml and in simian sarcoma virus-producing rat cells at 4 ng/ml. (iii) The efficiency of transformation of BalbC 3T3 cells by Moloney murine sarcoma virus, tested in a focus formation assay, was slightly enhanced by TPA. (iv) TPA inhibited the induction of endogenous virus formation in B cell mitogen-stimulated spleen cell cultures from BalbC mice.
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PMID:Diverse effects: augmentation, inhibition, and non-efficacy of 12-O-tetradecanoylphorbol-13-acetate (TPA) on retrovirus genome expression in vivo and in vitro. 617 39

Biphalin is a bivalent opioid analogue containing two tyrosine residues. We have examined the effect of biphalin's anti-retroviral potency in vitro using a murine model. Biphalin, in non-cytotoxic concentrations, suppressed in a dose-dependent fashion the replication of Friend leukemia virus (FLV) in Mus dunni cells as determined using a focus forming assay. FLV replication was substantially reduced by biphalin at 10(-4) M concentration. When biphalin was combined with 3'-azido-3'-deoxythymidine (AZT) the two acted synergistically in inhibiting FLV replication compared to either used alone. Using a reverse transcriptase (RT) assay, FLV RT levels also were noted to be reduced in the presence of biphalin. These observations indicate that biphalin possesses anti-retroviral activity in vitro, suggesting that this opioid peptide should be examined further in vivo to determine if it is a candidate for combined therapy with AZT and possibly other drugs for retrovirus infections including the human immunodeficiency virus (HIV).
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PMID:Inhibitory effect of biphalin and AZT on murine Friend leukemia virus infection in vitro. 981 90

We cloned and sequenced a mouse gene encoding a new type of membrane bound serine protease (epithin) containing a multidomain structure. The initial cDNA clone was found previously in a polymerase chain reaction (PCR)-based subtractive library generated from fetal thymic stromal cells, and the message was shown to be highly expressed in a thymic epithelial nurse cell line. A clone isolated from a severe combined immunodeficiency (SCID) thymus library and extended to its full length at the 5' end with the RACE technique contains an open reading frame of 902 amino acids. Based on the sequence of this clone, the predicted protein structure is a type II membrane protein with a C-terminal serine protease domain linked to the membrane by four low density lipoprotein receptor modules and two CUB domains. High message expression by northern blotting was detected in intestine, kidney, lung, SCID, and Rag-2(-/-) thymus, and 2-deoxyguanosine-treated fetal thymic rudiment, but not in skeletal muscle, liver, heart, testis, and brain. Sorted MHC class II+ and II- fetal thymic stromal cells were positive for expression by reverse transcriptase-PCR, whereas CD45(+) thymocytes were not. The gene was found in chicken and multiple mammalian species under low stringency Southern hybridization conditions. Under high stringency conditions, only a single gene per haploid genome was identified in the mouse. This gene, Prss14 (protease, serine, 14), was mapped to mouse chromosome 9 and is closely linked to the Fli1 (Friend leukemia integration 1) gene.
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PMID:Cloning and chromosomal mapping of a gene isolated from thymic stromal cells encoding a new mouse type II membrane serine protease, epithin, containing four LDL receptor modules and two CUB domains. 1019 18

Transcriptional control has been identified as a key mechanism regulating the formation and subsequent behavior of hematopoietic stem cells. We have used a comparative genomics approach to identify transcriptional regulatory elements of the LMO2 gene, a transcriptional cofactor originally identified through its involvement in T-cell leukemia and subsequently shown to be critical for normal hematopoietic and endothelial development. Of the 2 previously characterized LMO2 promoters, the second (proximal) promoter was highly conserved in vertebrates ranging from mammals to fish. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) expression analysis identified this promoter as the predominant source of transcription in hematopoietic tissue. Transient and stable transfections indicated that the proximal promoter was active in hematopoietic progenitor and endothelial cell lines and this activity was shown to depend on 3 conserved Ets sites that were bound in vivo by E74-like factor 1 (Elf1), Friend leukemia integration 1 (Fli1), and erythroblastosis virus oncogene homolog E twenty-six-1 (Ets1). Finally, transgenic analysis demonstrated that the LMO2 proximal promoter is sufficient for expression in endothelial cells in vivo. No hematopoietic expression was observed, indicating that additional enhancers are required to mediate transcription from the proximal promoter in hematopoietic cells. Together, these results suggest that the conserved proximal promoter is central to LMO2 transcription in hematopoietic and endothelial cells, where it is regulated by Ets factors.
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PMID:Fli1, Elf1, and Ets1 regulate the proximal promoter of the LMO2 gene in endothelial cells. 1599 90

Friend leukemia virus (FLV), a murine retrovirus, has been used as a model for elucidation of human immunodeficiency virus (HIV) immunopathogenesis and evaluation of anti-HIV drug effects for several decades. However, no method for direct detection of the plasma viral load has yet been reported. In this study, a TaqMan real-time quantitative reverse transcriptase PCR (qRT-PCR) assay was established for the rapid detection and quantitation of FLV. Measurement of the absolute FLV load was achieved through synthesis of a standard RNA from within the FLV envelope gene for generation of a standard curve. The assay allows quantitation over a range from 20 to 2 x 10(8) RNA copies per reaction in a two-step real-time quantitative reverse transcriptase PCR protocol. The relationships between the initially injected FLV dose and the plasma FLV load and spleen index were explored. Following this, the in vivo effects of zidovudine, adefovir dipivoxil, and entecavir on mice infected with FLV were evaluated. The results showed that the plasma FLV load was not proportional to the spleen index over the same FLV injection dosage series, although a trend was observed. When evaluated using plasma viral load, high dose (15 mg/(kg d)) adefovir dipivoxil was capable of significant inhibition of FLV replication in mice. The qRT-PCR assay described here allows specific, sensitive and direct detection of FLV and may also provide more precise measurement of FLV load.
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PMID:Development of a real-time quantitative reverse transcriptase PCR assay for detection of the Friend leukemia virus load in murine plasma. 1806 33

Biphalin, a dimeric enkephalin analog, is under investigation as a potential, long-lasting medication of pain associated with chronic diseases, like cancer or AIDS. The role of cytokines, and splenocytes in anti-Friend leukemia virus (FLV) activity of biphalin, a synthetic opioid, and AZT was investigated in vitro. Mouse splenocytes inhibited FLV replication in Mus dunni (Dunni) cells when they were added to the cell culture. This inhibitory effect of splenocytes also was evident when cells were combined with biphalin and AZT as measured using a focus-forming assay. Under cell-free conditions, recombinant interferon gamma (IFNgamma), interleukin 2 (IL-2) and IL-4 directly inhibited the FLV reverse transcriptase (RT) activity by 27% to 36%. IFNgamma at 0.005 pg to 500 ng inhibited FLVRT activity by 61% to 80%. Acombination of 250 ng IFNgamma and 50 mug biphalin resulted in a 94% reduction of FLVRT activity, as compared with 61% inhibition by IFNgamma alone. The combination of AZT and IFNgamma, IL-2 or IL-4 also induced a stronger suppression of FLV RT activity than either cytokine or AZT used alone. In addition, cloned RT from Moloney murine leukemia virus (MMLV) was directly sensitive to inhibition by biphalin. Thus, the anti-FLV effects of splenocytes in combination with biphalin and AZT in cell culture are likely mediated to a large degree by the direct effect of cytokines. This antiviral activity of splenocytes or cytokines combined with chemotherapy, biphalin, and/or AZT, could be used as a complementary therapy to current approaches for retroviral infection and benefit acquired immunodeficiency syndrome (AIDS) patients. In conclusion, biphalin applied primarily as a new medicine for chronic pain treatment in AIDS patients may play a significant beneficial role as a component of antiviral HIV multidrug therapies.
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PMID:Molecular assessment of the potential combination therapy of cytokines with biphalin and AZT for Friend leukemia virus infection in vitro. 1844 80


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