Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.7 (DNA polymerase)
 17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of several antiviral drugs on the reactivation of herpes simplex virus type 1 in explant cultures of latently infected mouse trigeminal ganglia was investigated. Phosphonoacetate and phosphonoformate, which act directly on the virus-induced DNA polymerase, require a drug concentration of 400 micrograms/ml for the inhibition of virus reactivation in latently infected ganglia. Arabinosyladenine and arabinosyladenine monophosphate, which are phosphorylated to triphosphates by cellular enzymes and inhibit virus synthesis either by blocking the DNA polymerase or by incorporation into viral DNA, require a concentration of only 100 micrograms/ml for the inhibition of the reactivation process. Drugs that are phosphorylated by the virus-induced thymidine kinase, such as acyclovir, arabinosylthymine, bromovinyldeoxyuridine, and three fluorinated pyrimidine nucleosides require the lowest drug concentrations for complete inhibition of virus reactivation in latently infected ganglia explant cultures. Our data suggest that the inhibition of virus reactivation is dependent not only on drug concentration, but also on the number of latently infected neurons in the ganglia.
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PMID:Effect of eight antiviral drugs on the reactivation of herpes simplex virus in explant cultures of latently infected mouse trigeminal ganglia. 620 91

The principal properties of the DNA polymerases of woodchuck hepatitis virus and human hepatitis B virus were compared. The enzymes of both viruses exhibited optimal activities in the same range of pH, ionic strength, and MgCl2 concentration. Like human hepatitis B virus DNA polymerase, the woodchuck hepatitis virus DNA polymerase was strongly inhibited by phosphonoformic acid but not by phosphonoacetic acid and aphidicolin. Similar inhibition patterns for both enzymes were observed with arabinofuranosyl nucleotides (9-beta-D-arabinofuranosyladenine-5'-triphosphate, 1-beta-D-arabinofuranosylcytosine-5'-triphosphate, 1-beta-D-arabinofuranosylthymine-5'-triphosphate) and dideoxythymidine triphosphate, whereas no effect was obtained with corresponding nucleosides. The therapeutic significance of these results and the relevance of the woodchuck as an experimental animal model for the study of human hepatitis B virus infections are discussed.
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PMID:Comparison of properties of woodchuck hepatitis virus and human hepatitis B virus endogenous DNA polymerases. 623 85

We have investigated the induction of Fc receptor (FcR) in different types of lymphoid cell lines (LCL) infected with herpes simplex virus (HSV). Subpopulations of certain of these LCL normally express FcR unrelated to herpetic infection. Differentiation of virus-induced FcR from that related to normal cell function was therefore possible. FcR detection was carried out by means of a rosette assay using ox erythrocytes coated with 7S immunoglobulin G (EA rosettes). Both HSV types 1 and 2 were found to induce FcR in B, T, and "null" (i.e., non-B, non-T) type LCL; however, in all the LCL tested, this HSV-induced FcR expression appeared to be more restricted in the responding T LCL than in responding B and null type LCL. In addition, kinetic experiments revealed that the time course of HSV-induced FcR expression differed among these LCL types tested. Interestingly, a number of LCL were resistant to HSV infection or restricted HSV gene expression, including expression of the viral products responsible for FcR induction. In all the responding HSV-infected LCL, induction of FcR always paralleled the expression of HSV antigens. Synthesis of HSV-induced FcR was shown to be inhibited by phosphonoacetic acid, an inhibitor of herpesvirus DNA polymerase activity, whereas FcR of non-HSV origin was found to be resistant to inhibitor. This would infer that HSV codes for an FcR which can be differentiated from that of cellular origin by using phosphonoacetic acid. Therefore, two different mechanisms of FcR synthesis may be suggested, one virus mediated and the second probably under cellular control. In addition, the data obtained using Epstein-Barr virus producer as well as isogeneic monoclonal cell lines, with and without the Epstein-Barr virus genome, indicated that the resident Epstein-Barr virus genome in the target cell did not have a detectable effect in the induction of FcR by HSV.
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PMID:Herpesvirus-lymphoid cell interactions: comparative studies on the biology of herpes simplex virus-induced Fc receptors in B, T, and "null" lymphoid cell lines. 624 24

Herpes simplex virus type 1 (HSV-1) infection of non permissive XC cells (a rat cell line transformed by Rous sarcoma virus) was studied. Using virus labeled with 3H-thymidine it was shown that adsorption is similar to that in a permissive system. By electron microscopy enveloped particles were observed in cytoplasmic vesicles in XC cells but not in the permissive system. However input viral DNA was degraded both in non permissive cells (XC) and permissive cells (HEp-2) and the degradation products were found incorporated into cellular DNA in the first case or into viral DNA in the second case. In the non permissive XC cells, it was possible to detect a small amount of incorporation of radioactive precursors into the viral DNA, identified by its buoyant density in CsCl of 1.726 g/cm3 and by hybridization with viral DNA. This DNA has the size of the native viral genome and its uptake of radioactive precursors was only partially inhibited by phosphonoacetic acid, a specific inhibitor of HSV-DNA polymerase. With permissive HEp-2 cells in the presence of such inhibitor, the obtained data are roughly the same as with XC cells, both in the presence or in the absence of phosphonoacetic acid. These results suggest that the observed viral DNA synthesis in XC cells is not a true replication but, further, a repair synthesis and, also, that the same events might take place in the permissive system before the onset of viral DNA replication.
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PMID:Herpes simplex type 1 infection of nonpermissive rat XC cells. 624 33

The diterpene ester promoter of mouse skin tumors, 12-O-tetradecanoylphorbol-13-acetate (TPA), efficiently induces Epstein-Barr virus (EBV)-associated DNA polymerase (DNA nucleotidyltransferase) activity in the EBV-producing lymphoblastoid cell line, P3HR-1. With the use of intervent dilution chromatography followed by sequential DEAE-cellulose and phosphocellulose column chromatography, the virus-associated enzyme has been isolated and purified 300-fold. The partially purified EBV DNA polymerase activity could be distinguished from cellular polymerases by its activation with salt and its degree of sensitivity to N-ethylmaleimide and phosphonoacetic acid. The enzyme showed maximum activity for copying activated calf thymus DNA in the presence of 100 mM ammonium sulfate. In the absence of salt, the enzyme utilized with high efficiency deoxyoligomer-homopolymer templates, but failed to copy poly(rA) . oligo(dT)10 and oligo(dT)10, showing that the enzyme had properties distinct from DNA polymerase gamma, reverse transcriptase, and terminal deoxynucleotidyltransferase. The partially purified enzyme is strongly inhibited by acyclovir triphosphate and thus has properties similar to herpes simplex virus DNA polymerase.
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PMID:Induction of Epstein-Barr virus-associated DNA polymerase by 12-O-tetradecanoylphorbol-13-acetate. Purification and characterization. 624 99

Two distinct loci that confer resistance to acycloguanosine (acyclo-Guo) in herpes simplex virus types 1 have been identified. The first locus is the gene for the virus-specific thymidine kinase (TK). Mutations that decrease TK activity also render the virus resistant to acyclo-Guo, and the level of resistance corresponds to the decrease in TK activity. acyclo-Guo resistance due to defective TK expression is recessive to the wild-type phenotype, acyclo-Guo-sensitive (ACGs). We term this locus ACGr-TK. The second locus is defined by the properties of a mutant, PAAr5, which is resistant to acyclo-Guo and to phosphonoacetic acid (PAA) yet exhibits wild-type TK activity. The acyclo-Guo-resistant locus in PAAr5 is separable from ACGr-TK mutations by recombination. Moreover, PAAr5 and ACGr-TK mutants can complement each other, producing drug-sensitive gene products which result in growth inhibition in the presence of acyclo-Guo. The acyclo-Guo resistance conferred by PAAr5 behaves as though it were codominant with the wild-type phenotype. This second acyclo-Guo-resistance locus is closely linked to the mutation specifying resistance to PAA. Resistance to PAA is thought to result from mutations in the gene for viral DNA polymerase. Thus, the close linkage of the ACGr and PAAr loci suggest that resistance to both drugs is specified by a mutant DNA polymerase. We term this second locus ACGr-PAA.
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PMID:Two distinct loci confer resistance to acycloguanosine in herpes simplex virus type 1. 624 31

Mutants of HSV which are resistant to acyclovir (acycloguanosine) have been isolated following serial passages of several herpes simplex virus (HSV) strains in the presence of the drug. The majority of the mutants isolated are defective in induction of thymidine kinase (TK) and this is consistent with the observation that independently isolated TK- viruses are naturally resistant to ACV. One mutant is described (SC16 R9C2) which is resistant in biochemically transformed cells which express HSV TK. This suggests that its resistance resides at a level other than TK. It is also resistant to phosphonoacetic acid, suggesting that the DNA polymerase locus may be involved. A further mutant is described [Cl (101) P2C5] which induces normal levels of TK, although the nature of resistance of this virus is not yet elucidated.
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PMID:Isolation and characterization of acyclovir-resistant mutants of herpes simplex virus. 625 85

Chromatin prepared from (14C)-thymidine pulse labelled cytomegalovirus-infected human fibroblasts 72 hours postinfection exhibited under appropriate conditions endogenous activity of (3H)-thymidine triphosphate incorporation which was relatively salt-resistant and phosphonoacetic acid-sensitive. Isopycnic centrifugation of the doubly labelled DNA in CsCl revealed that cell-free incoporation occurred into viral as well as into host cell DNA. Density labelling experiments with bromodeoxyuridine triphosphate suggested the incoporation into viral DNA to be due to replicative DNA synthesis. Chromatin from infected cells contained, in addition to cellular, viral DNA polymerase activity.
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PMID:DNA synthesis in chromatin preparations from human fibroblasts infected by cytomegalovirus. 625 65

We report on the properties of a temperature-sensitive mutant produced by transfection of cells with intact DNA and a specific DNA fragment mutagenized with low levels of hydroxylamine. The plating efficiency of the mutant at 39 degrees C relative to that at 33.5 degrees C was 5 X 10(-6). The pattern of polypeptides produced at the nonpermissive temperature was similar to that seen with wild-type virus in infected cells treated with inhibitory concentrations of phosphonoacetic acid in that alpha and beta polypeptides were produced, whereas most gamma polypeptides were either reduced or absent. Consistently, the mutant did not make viral DNA, although temperature sensitivity of the viral DNA polymerase could not be demonstrated. Marker rescue studies with herpes simplex virus type 2 (HSV-2) DNA mapped the mutant in the L component within map positions 0.385 and 0.402 in the prototype (P) arrangement of the HSV-1 genome. Analysis of the recombinants permitted the mapping of the genes specifying infected cell polypeptides 36, 35, 37, 19.5, 11, 8, 2, 43, and 44, but only the infected cell polypeptide 8 of HSV-2 was consistently made by all recombinants containing demonstrable HSV-2 sequences. Marker rescue studies with cloned HSV-1 DNA fragments mapped the temperature-sensitive lesion within less than 10(3) base pairs between 0.383 and 0.388 map units. Translation of the RNA hybridizing to cloned HSV-1 DNA, encompassing the smallest region containing the mutation, revealed polypeptide 8 (128,000 molecular weight), which was previously identified as a beta polypeptide with high affinity for viral DNA, and a polypeptide (25,000 molecular weight) not previously identified in lysates of labeled cells.
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PMID:Molecular genetics of herpes simplex virus. VII. Characterization of a temperature-sensitive mutant produced by in vitro mutagenesis and defective in DNA synthesis and accumulation of gamma polypeptides. 626 Sep 73

The Epstein--Barr (EB) virus induced DNA polymerase has been further purified and characterized with respect to nucleotide turnover activity, processiveness of synthesis, and interaction with phosphonoacetic acid (PAA). The polymerase as purified through denatured DNA--cellulose chromatography was inseparable from a labile nuclease activity associated with an equally labile DNA-dependent nucleotide turnover function. The EB virus induced DNA polymerase even in the absence of detectable nuclease or nucleotide turnover activity was less processive in its synthesis than were lymphocyte alpha polymerase or procaryotic polymerases, and this processiveness decreased with increasing purity of the enzyme. PAA was shown to inhibit nucleotide incorporation by the EB virus induced DNA polymerase in the presence of nuclease-activated native DNA template in the manner of a pyrophosphate analogue. Under conditions in which the concentration of 3'-hydroxyl termini in the template was more limited, PAA was not inhibitory. PAA likewise failed to significantly decrease the processiveness and the nucleotide turnover function of the polymerase.
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PMID:Characterization of purified Epstein--Barr virus induced deoxyribonucleic acid polymerase: nucleotide turnover, processiveness, and phosphonoacetic acid sensitivity. 626 79


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