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)

Nontoxic concentrations of Cyclosporin A (CyA) dose-dependently inhibited herpes simplex virus (HSV) production in resting monkey kidney cells. The block was at the step of virus DNA synthesis as assessed by [3H]thymidine incorporation and by dot blot hybridization of infected cell DNA using a cloned 32P-labelled HSV DNA fragment (BamHI X) as probe. This was further supported by analysis of HSV protein synthesis in the presence of CyA as assessed by sodium dodecyl sulphate polyacrylamide gel electrophoresis and Western blot. A relative accumulation of HSV alpha- (e.g., ICP 4) and beta 1-proteins (e.g., ICP 6 and 8) was found, whereas HSV gamma 1-proteins were slightly decreased and gamma 2-proteins were markedly decreased by CyA. The production of thymidine kinase and DNA polymerase was decreased when CyA was added to HSV infected cells. The sensitivity to CyA was not escaped by thymidine kinase nor DNA polymerase deficient mutants. Passage of HSV in presence of CyA did not result in induction of drug resistance.
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PMID:Inhibition of herpes simplex virus production in vitro by cyclosporin A. 130 45

Mouse macrophages grown from spleen cells were found to be very sensitive to the interferon (IFN) activity against herpes simplex virus type 1 (HSV-1). Therefore we have used these cells to investigate the level at which IFN blocks the replication of HSV-1. IFN treatment resulted in a strong inhibition of the induction of HSV DNA polymerase and other beta proteins. RNA hybridization experiments revealed that the amount of mRNA for the beta protein thymidine kinase was strongly reduced in IFN treated HSV-1 infected cells. Analysis of the effect of IFN on expression of the alpha genes indicated a strong inhibition of alpha protein synthesis. In contrast the synthesis of mRNA of the alpha protein ICP 4 was only moderately inhibited. The results indicate that IFN primarily acts on the translation of HSV alpha proteins.
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PMID:Synthesis of herpes simplex virus proteins and nucleic acids in interferon-treated macrophages. 242 81

The localization of ICP 4, ICP 8, DNA polymerase and alkaline exonuclease within herpes simplex virus type 1 (HSV)-infected cells has been examined by immunofluorescence using specific antibodies to these proteins. Cells were simultaneously counterstained with the DNA-binding fluorochrome 4,6-diamidino-2-phenylindole (DAPI) to reveal the intranuclear distribution of DNA. These studies showed that in the absence of virus DNA replication ICP 4, ICP 8 and DNA polymerase were diffusely distributed throughout the nucleus but during virus DNA replication these proteins accumulated at specific foci within the nucleus. Initially these foci were near the nuclear membrane but with continuing virus DNA replication they increased in size until the whole of the nucleus became affected. The increase in size of these foci was coincident with a redistribution of nuclear DNA and margination of chromatin at the nuclear membrane, as revealed by DAPI staining. The number of foci initially present in an infected cell was dependent on the multiplicity of infection. The distribution of ICP 4, ICP 8 and DNA polymerase within the nucleus was altered by treating the cells with DNase. The majority of alkaline exonuclease was diffusely distributed throughout the nucleus during virus DNA replication and did not localize at specific foci within the nucleus. Autoradiographic examination of the incorporation of [3H]thymidine in cells infected with HSV showed that viral DNA replication occurred in restricted areas within the nucleus that were similar, in terms of number, location and size, to the foci where ICP 4, ICP 8 and DNA polymerase accumulated. Furthermore, in cells blocked in mitosis following infection with HSV, ICP 4, ICP 8 and DNA polymerase, but not alkaline exonuclease, localized in areas outside the condensed chromatin structures. DAPI staining revealed the presence of DNA in these areas and, as such structures were never seen when uninfected cells had entered mitosis, it is suggested that this extrachromosomal DNA is of viral origin. These studies therefore suggest that ICP 4 is associated with progeny virus DNA and that while its intranuclear localization is initially at non-viral sites, as DNA replication proceeds so ICP 4 is recruited into areas of virus DNA transcription and replication.
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PMID:Intranuclear localization of herpes simplex virus immediate-early and delayed-early proteins: evidence that ICP 4 is associated with progeny virus DNA. 302 Jan 58

We have shown previously that the antiviral function of CD4+ T lymphocytes against murine cytomegalovirus (MCMV) is associated with the release of interferon-gamma (IFN-gamma). We now demonstrate that IFN-gamma and tumour necrosis factor alpha (TNF-alpha) display synergism in their antiviral activity. As little as 2 ng/ml of IFN-gamma and TNF-alpha reduced the virus yield by about three orders of magnitude. There was no effect on immediate early (IE) and early (E) gene expression as far as the candidate genes IE1, E1 and those encoding the major DNA-binding protein and the DNA polymerase were concerned. Late gene transcription, assayed by the candidate genes encoding glycoprotein B and the MCMV homologue of ICP 18.5, was blocked and MCMV DNA replication was found to be reduced but not halted. The most prominent finding of the cytokine effect, seen by electron microscopy, was an alteration of nucleocapsid formation. Altogether, the synergism is multifaceted and acts at more than one stage during viral morphogenesis. Because the cytokines clearly do not act at an early stage of infection we conclude that the mode of cytokine activity differs between alpha- and betaherpesviruses.
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PMID:Late phase inhibition of murine cytomegalovirus replication by synergistic action of interferon-gamma and tumour necrosis factor. 811 18

The iridovirus isolate termed cricket iridovirus (CrIV) was isolated in 1996 from Gryllus campestris L. and Acheta domesticus L. (both Orthoptera, Gryllidae). CrIV DNA shows distinct DNA restriction patterns different from those known for Insect iridescent virus type 6 (IIV-6). This observation led to the assumption that CrIV might be a new species within the family Iridoviridae. CrIV can be transmitted perorally to orthopteran species, resulting in specific, fatal diseases. These species include Gryllus bimaculatus L. and the African migratory locust Locusta migratoria migratorioides (Orthoptera, Acrididae). Analysis of genomic and host range properties of this isolate was carried out in comparison to those known for IIV-6. Host range studies of CrIV and IIV-6 revealed no differences in the peroral susceptibility in all insect species and developmental stages tested to date. Different gene loci of the IIV-6 genome were analyzed, including the major capsid protein (274L), thymidylate synthase (225R), an exonuclease (012L), DNA polymerase (037L), ATPase (075L), DNA ligase (205R) and the open reading frame 339L, which is homologous to the immediate-early protein ICP-46 of frog virus 3. The average identity of the selected viral genes and their gene products was found to be 95.98 and 95.18% at the nucleotide and amino acid level, respectively. These data led to the conclusion that CrIV and IIV-6 are not different species within the Iridoviridae family and that CrIV must be considered to be a variant and/or a novel strain of IIV-6.
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PMID:Comparative analysis of the genome and host range characteristics of two insect iridoviruses: Chilo iridescent virus and a cricket iridovirus isolate. 1180 40