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:2.7.1.21 (thymidine kinase)
7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Herpes simplex virus (HSV) type 1 can be differentiated from HSV type 2 on the basis of the sensitivity to 2'-deoxythymidine-5'-monophosphate of thymidine kinase induced in primary rabbit kidney cells. Whereas thymidine kinase induced by five strains of HSV type 1 (TK 1) is stimulated by suitable concentrations of 2'-deoxythymidine-5'-monophosphate, thymidine kinase induced by eight strains of HSV type 2 (TK 2) is inhibited. On the other hand, TK 2 is strongly inhibited by 2'-deoxythymidine-5'-triphosphate and by 2-bromo-2'-deoxyuridine-5'-triphosphate. The investigation of TK induced by six freshly isolated strains of HSV cross-reacting in neutralisation tests revealed two strains which induced TK 1 and two strains which induced TK 2. Two other strains induced thymidine kinase, the activity of which under the influence of these thymidine analogues was between that of TK 1 and TK 2. The properties of thymidine kinase remained constant after cloning the virus and thus is a genetically fixed trait due to recombination which could well occur in vivo.
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PMID:Biochemical classification of herpes simplex virus types 1 and 2, and of intermediate strains on the basis of different susceptibilities of thymidine kinase to thymidine analogues. 0 38

Herpes simplex virus type 1, strain Kupka, did not replicate in chick embryo fibroblasts (CEF), but the infection was followed by the development of cytopathic changes. This effect could be abolished by UV irradiation of the virus. Virus-induced thymidine kinase was synthesized in the infected cells reaching a maximum level at 24 hours post infection (p.i.). In the presence of cytosine arabinoside, thymidine kinase synthesis was enhanced. This suggested that the late (post-replicative) viral function, which turns off thymidine kinase synthesis, was expressed in the infected CEF untreated with the drug. HSV type 1 laboratory strains Kupka and KOS were capable of inducing the synthesis of virus-specific DNA in CEF. But in CEF infected with fresh type 1 virus isolates replication of viral DNA was not observed.
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PMID:Syntheses of virus-induced thymidine kinase and viral DNA in herpes simplex type 1 virus-infected chick embryo fibroblasts. 1 14

5-Carboxy-2'-deoxyuridine (5-COOH-2'-dUrd) is a product of the base-catalyzed hydrolysis of 5-trifluoromethyl-2'-deoxyuridine. Hydrolysis of 5-trifluoromethyl-2'-deoxyuridine to 5-COOH-2'-dUrd in phosphate-buffered saline was kinetically first order and was pH dependent. At 37 degrees C and pH 7.0, 7.5, and 8.0, hydrolysis occurred with rate constants of 4.19 x 10(-5), 9.30 x 10(-5), and 1.61 x 10(-4) s(-1), respectively, with corresponding half-lives of 45.7, 20.6, and 11.9 h. 5-COOH-2'-dUrd inhibited growth of HEp-2 cells by 21, 67, and 91% at 1.0, 10, and 100 muM, with no antiviral activity against herpes simplex virus type 1 or herpes simplex virus type 2 at 1.0 or 10 muM. Partial reversal of cytotoxicity in HEp-2 cells was achieved with orotidine, uridine, deoxythymidine, or deoxycytidine, whereas complete reversal of cytotoxic effects was achieved with simultaneous addition of deoxythymidine, deoxycytidine, and uridine. 5-COOH-2'-dUrd at 50 muM inhibited incorporation of [(14)C]orotate into RNA and DNA by 65 and 27%, respectively. 5-COOH-2'-dUrd had no effect on the incorporation of [(3)H]uridine into DNA or RNA. Because of the structural similarities to deoxythymidine, 5-COOH-2'-dUrd was tested as an inhibitor of deoxythymidine kinase. 5-COOH-2'-dUrd was neither a substrate nor an inhibitor of herpes simplex virus type 1 induced deoxythymidine kinase or HEp-2 cell deoxythymidine kinase. Based on these observations, the metabolic block induced by 5-COOH-2'-dUrd has been localized to the de novo pyrimidine biosynthetic pathway between orotate phosphoribosyl transferase and orotidine 5'-phosphate decarboxylase.
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PMID:Biological effects of 5-carboxy-2'-deoxyuridine: hydrolysis product of 5-trifluoromethyl-2'-deoxyuridine. 2 91

Four strains of herpes simplex virus (HSV) were isolated from two patients with recurrent herpes keratitis who failed to respond to 5'-iodo-2'-deoxyuridine (IDU) treatment. Two of the four isolates were highly resistant to IDU in cell culture and the other two isolates were more susceptible to IDU than an HSV-1 laboratory strain. From each patient, an IDU-resistant and an IDU-susceptible virus was isolated. All 4 isolates possessed the ability to induce the thymidine kinase (TK) activity in cell lines lacking that activity. All the isolates were type 1 HSV, since the filamentous structures, recognized as a biological marker of type 2 HSV, were not observed in infected cells.
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PMID:Analysis of herpes simplex virus isolated from patients with recurrent herpes keratitis exhibiting "treatment-resistance" to 5-iodo-2'-deoxyuridine. 4 35

Herpes simplex virus (HSV)-related antigens have been demonstrated in the nuclei and cytoplasm of human and mouse cells biochemically transformed by ultraviolet light-irradiated HSV. This was accomplished by using peroxidase/anti-peroxidase immunological staining and indirect immunofluorescence with rabbit antisera that had high neutralizing titers against the HSV-specific thymidine kinase activity and virus infectivity. HSV-1 antisera reacted with antigens in cells biochemically transformed by type 1 HSV, but not with those of cells biochemically transformed by type 2 HSV. Similarly, HSV-2 antisera reacted with antigens in cells biochemically transformed by HSV-2, but not with those in cells biochemically transformed by HSV-1. In contrast, herpes virus-related antigens were detected in cells cytolytically infected with HSV-1 and with HSV-2 by either type 1 or type 2 HSV antisera. These observations suggest that the antigens detected in the biochemically transformed cells were a type-specific subset of the HSV-related antigens synthesized in cells undergoing productive infection by HSV-1 and HSV-2.
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PMID:Detection of herpes simplex virus-related antigens in the nuclei and cytoplasm of biochemically transformed cells with peroxidase/anti-peroxidase immunological staining and indirect immunofluorescence. 7 Dec 79

The kinetics of formation, the stability at 40 degrees C and the serological properties of thymidine kinase and deoxycytidine kinase activities induced by herpes simplex virus have been examined. The results are consistent with the hypothesis that both activities are carried on the same molecule-a deoxypyrimidine kinase. Mutants deficient in deoxypyrimidine kinase have been used to produce, by absorption of general antisera, deoxypyrimidine kinase-specific antisera. Using immunoprecipitation and SDS-polyacrylamide gel electrophoresis, only one size of polypeptide (mol. wt. 42400 plus or minus 200) has been found, constituting the type 2 enzyme. This is close to published values for the type i enzyme but co-electrophoresis demonstrated that the polypeptide of the type i enzyme was slightly bigger.
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PMID:Deoxypyrimidine kinases of herpes simplex viruses types 1 and 2: comparison of serological and structural properties. 16 87

A cell line that normally supports the replication of herpes simplex virus types 1 and 2 became resistant to these viruses after transformation by simian adenovirus 7. Kinetic studies of the mechanism of resistance demonstrated that both herpesviruses were able to attach to the transformed cells and express some early genomic functions, as demonstrated by the presence of low levels of viral thymidine kinase. However, isopycnic centrifugation studies of the abortive system failed to detect viral deoxyribonucleic acid synthesis, whereas indirect immunofluorescent studies of viral proteins revealed that less than 10 per cent of the cells contained these viral macromolecules at any given time. Collectively the data suggest that after transformation by simian adenovirus 7 these cells are altered so as to render them resistant or incapable of supporting the growth of herpes simplex virus types 1 and 2. The results further suggest that the block occurs after viral absorption and prior to viral deoxyribonucleic acid synthesis.
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PMID:Adenovirus-transformed cells restrict Herpes simplex virus replication. 16 98

The effect of Rolly No. 11 strain herpes simplex virus infection of HeLa cells in culture on deoxynucleotide metabolism and the level of various enzymes concerned with the biosynthesis of DNA has been investigated. Of 18 enzyme activities studied, thymidine kinase, DNA polymerase and deoxyribonuclease were markedly augmented, a finding in agreement with previous reports. Deoxycytidine kinase, ribonucleotide reductase, thymidylate kinase and deoxycytidylate deaminase activities, in contrast with previous reports, did not increase; the activities of the other enzymes studied, also did not increase. Whereas most of the radioactivity derived from [14-C] thymidine in the acid-soluble fraction of the uninfected cells was present as deoxythymidine triphosphate, that present in the infected cells was primarily in the form of deoxythymidine monophosphate. Thus, in the infected cell deoxythymidylate kinase is a rate-limiting enzyme in the biosynthesis of deoxythymidine triphosphate. A marked increase in the pools of the four naturally occurring deoxynucleoside triphosphates (dTTP, dCTP, dATP, dGTP) was found. The rate of formation of the virus-induced enzymes was determined, as were the various nucleoside triphosphate pools and the other phosphorylated derivatives of thymidine; a maximum was reached for all these csmponents between 6 to 8 h post infection. Although an apparent greater synthesis of DNA occurred in the uninefected cells, when the specific activity of the radioactive deoxythymidine triphosphate was taken into account, there was actually a greater rate of DNA synthesis in the infected cells, with the peak at 8 h post infection.
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PMID:Deoxyribonucleotide metabolism in Herpes simplex virus infected HeLa cells. 16 49

Antiserum prepared against herpes simplex virus type 1 (HSV-1)-infected L cells, i.e., lytic antiserum, was shown by an indirect immunofluorescence test to stain 90 percent of HSV-transformed L or HeLa cells. Immunofluorescence in these cells was always most intense in the perinuclear cytoplasmic region. Similar results were obtained with antiserum prepared against HSV-transformed L cells. These data indicate that HSV-transformed cells (both L and HeLa) express HSV-related antigens. Antiserum prepared against HSV-1-transformed L cells, i.e., transformed-cell antiserum, was found to agglutinate purified HSV type 1 virions but failed to neutralize infectivity. This suggests that HSV-1 structural antigens are expressed in HSV-1-transformed L cells. Immunodiffusion studies showed that at least two HSV-related antigens could be demonstrated with antigens from HSV-1-transformed L cells and transformed-cell antiserum. These two antigens were shown to be present in all clonal lines of HSV-1-transformed cells examined, six L cell lines and one HeLa cell line. Therefore, we conclude that transformation of cells by HSV-1, which is known to be associated with acquisition of viral thymidine kinase, must also be associated with the presence of these two antigens. We performed experiments showing that there are species of HSV-related antibody in HSV-transformed cell antiserum that could not be absorbed out with antigens from HSV-infected L cells. Antibodies present in lytic antiserum were completely removed by antigen preparations from cells lytically infected with HSV-1. Also, lytic antiserum failed to block HSV-related staining of transformed L cells in a direct immunofluorescence test. These results are compatible with one of two notions: either (i) certain genes are expressed during transformation that are not expressed during lytic infection, or (ii) these genes are expressed to a much more reduced extent during lytic infection than in transformed cells.
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PMID:Presence of herpes simplex virus-related antigens in transformed L cells. 16 95

Twelve temperature-sensitive (ts) mutants of herpes simplex virus type 1 (HSV-1), representing seven complementation groups, were isolated subsequent to 5-bromodeoxyuridine mutagenesis. These mutants were identified by their inability to replicate in a line of monkey (CV-1) cells at 39 C. Seven of these mutants, representing six complementation groups, induced thymidine kinase (tk) and transformed Ltk- cells, a line of mouse L cells lacking tk, to a tk+ phenotype at both the permissive (34 C) and nonpermissive (39 C) temperatures. Thus, the defective cistrons in these six complementation groups, although necessary for lysis, have no essential function in this transformation system. Transformation by these 12 mutants was dependent on prior UV irradiation. Infection of cells with unirradiated virus under conditions which did not permit virus replication was not sufficient to allow cell transformation. Five mutants, representing two complementation groups, were tk- and were incapable of causing the tk--to-tk+ transformation at either 34 C of 39 C. The tk defects in these mutants are probably unrelated to the ts defects, since one of these complementation groups contains a tk+ member. Therefore, transformation of Ltk- cells to a tk+ phenotype by HSV-1 requires an active viral tk gene. One complementation group was represented by a single tk- member. The role of this cistron in transformation remains undetermined since the primary block to transformation is presumed to be the tk- phenotype. Mutants representing the seven complementation groups were unable to replicate at 39 C in two lines of HSV-1-transformed cells, indicating that the activities of resident wild-type copies of the defective cistrons, if present, could not be detected by complementation.
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PMID:Temperature-sensitive mutants of herpes simplex virus type 1 defective in lysis but not in transformation. 16 2


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