Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

HeLa cells generally do not respond well to interferon (IFN). We have used is-1, an IFN-sensitive mutant of mengovirus, to select a clone of IFN-responsive HeLa cells (F-H12). At moderate levels of human alpha/beta IFN, is-1 yields were fivefold lower in these cells than in similarly protected control cells. In contrast, wild-type mengovirus, vesicular stomatitis virus and a wild-type and thymidine kinase-negative strains of herpes simplex virus type 1 grew equally well in both cell lines. By a cell survival assay, the F-H12 line was up to 100 times more responsive to IFN than the parental line when challenged by is-1. 2'-5'-Oligo(A)-dependent endonuclease activity was the same in both lines. These observations cannot be accounted for by enhanced induction of IFN following infection.
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PMID:Selection and characterization of an interferon-responsive clonal cell line of HeLa cells. 302 28

A mouse cell line (Ltk-aprt-) which is resistant to the anti-viral effects of interferon also has a reduced ability to synthesize metallothionein on exposure to cadmium. Like the ability to respond to interferon, cadmium-induced metallothionein synthesis is restored to wild-type levels in clones obtained by introducing a thymidine kinase gene into Ltk-aprt-cells. Transfection of other genes does not have such an effect. Since metallothionein expression is also activated by interferon the results suggest that the regulation of several genes which are responsive to interferon can be modulated by specific sequences present in the Herpes virus thymidine kinase gene.
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PMID:Activation of metallothionein expression is potentiated by DNA sequences present in the herpes simplex virus thymidine kinase gene. 303 84

Sensitivity of herpes simplex virus (HSV) isolates, from patients with recurrent infections, to human fibroblast beta interferon (IFN), was tested in vitro. Among 25 HSV strains, 12 were HSV-1, isolated from facial and labial lesions, and 13 were HSV-2 isolated from genital lesions. Viral sensitivity to IFN was examined on epithelial MB cell line by yield reduction and plaque reduction and close correspondence between the two methods was observed. Most of HSV-1 isolates were in the same range of sensitivity to IFN, while HSV-2 isolates varied in sensitivity and differences approached statistical significance (P = 0.14). No correlation was found between various biological properties, such as plaque size, virulence in baby mice, growth at different temperatures, thymidine kinase activity in the presence or absence of IFN and sensitivity to IFN. Application of beta IFN containing cream reduced clinical symptoms in most of the patients. However, larger numbers of patients should be evaluated in order to conclude whether in vitro sensitivity correlates to clinical improvement.
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PMID:Sensitivity in vitro of herpes simplex virus isolates to human fibroblast interferon. 303 88

An EcoRI fragment (1.83 Kb) of human DNA containing B1-interferon coding sequences was cloned in the episomal eukaryotic vector pBK-TK. The recombinant plasmid was transfected into thymidine kinase-deficient HeLa cells. Thymidine kinase-positive transformants were obtained and the cells were found to express B-interferon both constitutively and after induction with Newcastle Disease Virus or poly(rI)-poly(rC). The recombinant plasmid was present in stably transformed HeLa cells in an episomal state in hundreds of copies per cell.
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PMID:Constitutive and inducible expression of cloned human interferon-b1 gene in HeLa cells through an episomal eukaryotic vector. 306 79

We assayed fragments of the 5' flanking sequence of the human 2-5A synthetase gene for their ability to respond to interferon-alpha (IFN) and platelet-derived growth factor (PDGF). Transient transfection assays identified a 40-base pair fragment, which, regardless of orientation, could confer IFN-inducibility on the thymidine kinase promoter. This same fragment was active in monkey and mouse cells and in the latter was responsive to PDGF. The effect of PDGF could be inhibited by anti-interferon antibodies. Gel retardation assays, using the 40-base pair probe, detected the presence of IFN-modulated DNA-binding factors in nuclear extracts from monkey cells. In mouse cells both IFN and PDGF induced the binding of nuclear factors to a synthetic 2-5A synthetase response sequence. Thus, both IFN and growth factors directly or indirectly modulate the binding of nuclear factors to the same region of the 2-5A synthetase gene.
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PMID:Interferon and growth factor modulation of nuclear factors binding to 5' upstream elements of the 2-5A synthetase gene. 324 Oct 14

A human gene encoding an interferon-induced 15-kDa protein has been isolated from a genomic library. The gene appears to be single-copy and is composed of two exons, the first of which contains the ATG translation initiation codon. In vitro nuclear run-on assays showed that the transcription rate of the gene is stimulated after interferon treatment. To analyze transcriptional regulatory sequences, we constructed recombinant plasmids for use in transient transfection assays of HeLa cells. Constructs containing 115 nucleotides 5' to the transcription initiation site were found to be fully inducible by interferon. Assays of deletion mutants identified a critical element for interferon induction located between -115 and -96, just upstream of the "CCAAT box." Moreover, a DNA fragment including this region can confer interferon inducibility on a heterologous promoter (thymidine kinase) when cloned in either orientation upstream of the gene or downstream of the gene. These are properties characteristic of an enhancer element that is active only after treatment with interferon. This regulatory sequence may be shared by a group of interferon-induced genes, since a very similar sequence is present within the functional region near the RNA start site of another interferon-induced gene.
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PMID:Interferon-induced transcription of a gene encoding a 15-kDa protein depends on an upstream enhancer element. 347 54

The rodent established cell lines LTk- and NIH 3T3 have been used as recipients in gene transfer experiments to study the effect of interferon treatment on the genetic and oncogenic transformation by several genes of viral and cellular origin. Our results show that interferon severely inhibits, to a similar extent, the stable transformation of Ltk- and NIH 3T3 cells by the chicken thymidine kinase (tk) gene, Ecogpt gene, simian virus 40, v-Ha-ras, and human c-Ha-ras and c-Ki-ras oncogenes. These results are consistent with an inhibition by interferon at the level of stabilization or integration, or both, of exogenous DNA sequences in the recipient cells, with an apparent effect on gene expression.
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PMID:Inhibitory effect of interferon on the genetic and oncogenic transformation by viral and cellular genes. 397 79

Early antiviral drugs, such as idoxuridine and vidarabine, are less effective than newer drugs, such as trifluorothymidine and acyclovir. However, trifluorothymidine is less subject to the development of drug-resistant strains and can be administered topically as a clear drop, which increases patient compliance. Acyclovir has low toxicity and is selective for virus-infected cells because it must be phosphorylated by the viral thymidine kinase to become active. However, drug-resistant strains are produced relatively easily in vitro and may also develop in man with long-term use. To date, no antiviral drug alone has been shown to be effective in the treatment of stromal disease, and no antiviral drug is able to eradicate virus latent in the ganglia and thereby prevent recurrent herpetic infections. Combinations of antiviral drugs and antiviral drugs and interferon are being tested for enhanced efficacy in the treatment of ocular herpetic disease, and for prophylactic effects. The development of recombinant interferons has reduced cost and increased availability, but the effects of the 'manufactured' interferon are not identical to those of natural human leukocyte interferon in all experimental situations.
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PMID:Virus chemotherapy: antiviral drugs and interferon. 608 32

The effect of interferon on the biochemical transformation of thymidine kinase-deficient cells by UV-inactivated herpes simplex virus type 2 has been studied. Transformation was much less sensitive to the action of interferon than virus multiplication. However, the continuous presence of a high dose of interferon (2,000 U) inhibited transformation almost completely. Although we could not differentiate between the effect of interferon on fixation and expression of the virus thymidine kinase gene, data suggest that the inhibitory effect of interferon on transformation might be partially due to the suppression of virus thymidine kinase expression.
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PMID:Inhibition of herpes simplex virus type 2-induced biochemical transformation by interferon. 615 51

We have obtained hybrids of PCC4-aza 1, a mouse embryonal carcinoma stem cell line, and two different thymidine kinase deficient mouse cell lines. We have examined the ability of the parental and hybrid cells to produce interferon after infection with the Newcastle Disease virus and to enter the antiviral state when treated with mouse interferon. The interferon system of PCC4-aza 1 is inactive; this characteristic is recessive in the hybrids obtained.
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PMID:Characteristics of the interferon system of an embryonal carcinomal cell are recessive in intraspecific somatic cell hybrids. 615 4


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