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:2.7.7.7 (DNA polymerase)
17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Low concentrations of adenine arabinoside inhibited growth of two Epstein-Barr virus producer cell lines in culture, while not significantly affecting a nonproducer cell line and a B-cell-negative line. These observations were extended to include freshly infected cells. Mitogen-stimulated human umbilical cord blood lymphocytes were unaffected by the drug at concentration levels that inhibited [3H]thymidine incorporation into the DNA of Epstein-Barr virus-stimulated cells. DNA synthesis in Epstein-Barr virus-superinfected Raji cells was also adversely affected by adenine arabinoside. However, these same low concentrations of adenine arabinoside in the triphosphate form produced less effect on DNA synthesis in nuclear systems and DNA polymerase assays than on growth or DNA synthesis in whole cells. Therefore the effects reported here of low concentrations of the drug on whole cells may be only in part related to DNA polymerase inhibition. The work reported here suggests that adenine arabinoside has multiple sites of action in infected cells.
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PMID:Effects of adenine arabinoside on lymphocytes infected with Epstein-Barr virus. 21 77

The present paper reports on the induction of two cell surface markers on human lymphoid cells following herpes simplex virus (HSV) infection. While both primary and chronic infections of human lymphoid cells led to the induction of receptors for the Fc region of 7S IgG, chronic HSV infection was also characterized by the induction of surface-bound IgM. Surface and intracellular Fc receptors were detected in the human lymphoid cell line, Raji, infected with HSV types 1 and 2. Under optimal conditions with a multiplicity of infection (m.o.i.) of 50 to 100 p.f.u. per cell, this marker was inducible in only about 53% of the infected cells. Kinetic studies revealed the appearance of these receptors at around 5 h following HSV infection and they reached a plateau 16 to 18 h p.i. Interestingly, this Fc receptor expression (i.e. percentage of positive cells) was found to be similar in primary and chronically HSV-infected Raji cells. Both human leukocyte interferon and phosphonoacetic acid (PAA), an inhibitor of herpesvirus DNA polymerase activity, effectively inhibited Fc receptor synthesis during primary HSV-infection and these two agents suppressed its induction in chronically HSV-infected Raji (Raji-HSV) cells. This inhibitory or suppressive effect, particularly of PAA, suggests that this HSV-induced Fc receptor may represent a late virus function in the infected cell. Unlike primary HSV infection, about 80% of the chronically HSV-infected Raji cells were found to express surface-bound IgM. This IgM induction was suppressed by long-term interferon treatment but not with PAA-treatment. Superinfection studies of interferon and PAA-treated Raji-HSV cells indicate that only the former would develop Fc receptors suggesting a protective role of this IgM against superinfection by HSV.
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PMID:Studies on the induction of IgG-Fc receptors and synthesis of IgM in primary and chronically-infected lymphoid (Raji) cells by herpes simplex virus. 23 Feb 88

While both primary and chronic herpes simplex virus (HSV) in vitro infections of a Burkitt's lymphoma-derived cell line (Raji) were similarly characterized by the induction of IgG-Fe receptors in about 50% of cells, the persistent HSV infection of Raji cells was also accompanied by an induction of surface-bound IgM in approximately 80% of cells. This IgM induction was suppressed by treating the infected cells with interferon, but not with phosphonoacetic acid, an inhibitor of herpes virus DNA polymerase activity. The fact that only the cell population which had lost this IgM expression was superinfectable would suggest that this Ig may play a protective role (e.g. antibody activity?) against HSV.
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PMID:Interferon-sensitive expression of membrane-bound IgM on a human lymphoid B cell line persistently infected with herpes simplex virus. 31 9

The gene (pol) encoding the Epstein-Barr virus (EBV) DNA polymerase is a member of the "early" class of viral genes which are expressed shortly after activation of latent virus infection. First, mRNA from the EBV-producing cell line, B95-8, treated with 12-O-tetradecanoylphorbol-13-acetate and sodium butyrate to induce lytic replication and expression of this gene was analyzed. Northern (RNA) analysis revealed a message of 3.7 kb found only in induced cells. 5' mapping of pol mRNA by S1 nuclease and primer extension analyses indicates that transcription initiates at tightly clustered sites within a G + C-rich region 126 bp upstream of the open reading frame. The same initiation region was identified in two other EBV-infected cell lines, P3HR1 and Raji, after induction. Second, a 1.29-kb genomic fragment containing this region, when cloned upstream of the chloramphenicol acetyltransferase reporter gene, demonstrated promoter activity in lymphoid cells cotransfected with pEBV-RZ, a genomic expression construct that includes genes for the EBV immediate-early transactivator proteins, BZLF-1 and BRLF-1. Within the upstream 1.29-kb sequence, two regions of 140 bp and 101 bp appear to be needed for promoter activity. These results demonstrate that unlike most EBV genes studied thus far, the pol gene contains multiple transcriptional start sites. The upstream regulatory region of the promoter for the pol gene does not contain canonical promoter elements such as TATA and CAAT boxes and, furthermore, is not constitutively active but requires transactivation by two or more viral proteins.
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PMID:Regulation of the Epstein-Barr virus DNA polymerase gene. 131 4

In order to identify the gene encoding the Epstein-Barr virus (EBV) DNA polymerase, a portion of the BamHI-A fragment containing the fifth leftward open reading frame (BALF5) of the EBV genome was cloned into SP6 and T7 promoter-containing vectors for in vitro transcription-translation. The RNA synthesized in vitro was used to program rabbit reticulocyte lysates, which were analyzed for the synthesis of the putative polymerase polypeptide (110 kDa) and assayed directly for EBV DNA polymerase activity. The polypeptide synthesized by the full-length BALF5 genomic fragment had a molecular mass of 110 kDa. 5'-truncated BALF5 with the first and second ATGs deleted produced 95- and 83-kDa polypeptides, respectively. All three translation products were enzymatically active and displayed resistance to high salt concentrations. The identity of the largest polypeptide as the viral polymerase was established by (i) immunoprecipitation with EBV-positive sera from patients with nasopharyngeal carcinoma and by a rabbit polyclonal antiserum prepared with a synthetic peptide derived from the DNA sequence of BALF5; (ii) identification of a polypeptide of identical size (110 kDa) immunoprecipitated from superinfected Raji cell extracts by these antibodies; and (iii) salt-resistant enzymatic activity which was neutralized by the rabbit EBV antiserum. Thus, BALF5 encodes a functional polymerase identical to that induced in superinfected Raji cells.
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PMID:Identification and functional characterization of Epstein-Barr virus DNA polymerase by in vitro transcription-translation of a cloned gene. 185 46

A cloned plasmid, pmyc(H-K), containing sequences derived from human c-myc gene replicated in vitro in Raji nuclear extract in a semiconservative manner. Using this system, it was found that phosphatidylinositol and cardiolipin strongly inhibited the replication of pmyc(H-K) in vitro, whereas other phospholipids, i.e., phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, phosphatidic acid, and sphingomyelin, had no appreciable effect. The concentrations of phosphatidylinositol and cardiolipin producing 50% inhibition of the replication were 4.6 and 5.4 microM, respectively. Phosphatidylinositol and cardiolipin inhibited the relaxation of pmyc(H-K) supercoiled DNA, but showed little or weaker effects on DNA polymerase alpha and topoisomerase II in Raji nuclear extract. These results suggest that phosphatidylinositol and cardiolipin antagonize the replication of pmyc(H-K) in vitro, through, at least in part, the interaction with topoisomerase I.
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PMID:Phospholipid modulates in vitro replication of autonomous replicating sequence from human cells. 285 2

Selective DNA extraction and hybridization procedures were used to estimate the relative number of covalently closed circular viral genomes in cultures of Epstein-Barr virus (EBV)-transformed cells. In virus-producing P3HR-1 cultures that were exposed for 11 days to phosphonoacetic acid or to acyclovir, the content of covalently closed circular EBV DNA was reduced ca. 70% relative to a control culture without drug. The EBV plasmid content of Raji, a virus nonproducer cell line, was not reduced by exposure to these compounds. When P3HR-1 cultures were exposed to 12-O-tetradecanoylphorbol-13-acetate, the number of circular genomes per cell increased. These findings indicate that two enzyme activities synthesize circular EBV DNA and that the virus-associated DNA polymerase synthesizes most of the circular EBV DNA in a virus producer culture. It is suggested that the circular genomes synthesized by the viral enzyme are intermediates in the syntheses of linear virus DNA.
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PMID:The circular intracellular form of Epstein-Barr virus DNA is amplified by the virus-associated DNA polymerase. 298 82

The 145-kDa molecule that has been identified as the C3d receptor CR2 was isolated from lysates of Raji cells by affinity chromatography by using the monoclonal antibody (MoAb)HB-5. The purified protein was incorporated into 14C-phosphatidylcholine liposomes by deoxycholate dialysis followed by flotation on discontinuous sucrose gradients. Incorporation of the receptor was verified by testing the gradient fractions for CR2 by an enzyme-linked immunosorbent assay. Liposomes were shown to be unilamellar vesicles ranging in diameter from 25 to 100 nm by electron microscopy. The external orientation of CR2 in the membranes was demonstrated by immunoelectron microscopy. The functional activities of liposomes containing CR2 and liposomes without protein were compared. CR2 liposomes bound to EC3d, but not to E, and this binding was inhibited by the anti-CR2 MoAb OKB7 and by a MoAb specific for C3d. Control liposomes failed to bind to either E or EC3d. The ability of CR2 to function as a receptor for Epstein Barr virus (EBV) was tested in two ways. First, CR2 liposomes bound to B95-8, a cell line expressing EBV membrane antigens, but not to B95-8 cells treated with the viral DNA polymerase inhibitor phosphonoformic acid. Second, liposomes containing CR2 were shown by ultracentrifugal analyses to bind directly to purified EBV, and this binding was also inhibited by OKB7. Control liposomes did not bind to B95-8 cells or to EBV. These findings show that CR2 purified from detergent extracts of Raji cells can be reconstituted into lipid membranes with maintenance of its dual functions as a receptor for C3d and EBV.
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PMID:Incorporation of the purified Epstein Barr virus/C3d receptor (CR2) into liposomes and demonstration of its dual ligand binding functions. 300 15

Virus-nonproducer Raji cells, when induced to early antigen synthesis by 12-O-tetradecanoyl-phorbol-13-acetate and sodium butyrate, showed an increase in DNA polymerase activity. This enzyme has the characteristics of a typical Epstein-Barr virus DNA polymerase with regard to chromatographical pattern and biological properties: it is eluted from DEAE-cellulose at 0.08 M NaCl, has a high salt resistance, is sensitive to phosphonoacetic acid and phosphonoformate, and shows a substrate preference for poly(dC)-oligo(dG12-18). The resistance of Epstein-Barr virus polymerase activity to aphidicolin is a property distinct from that of HSV DNA polymerase. Viral DNA polymerase activity increases in the absence of Epstein-Barr virus DNA replication, indicating that this enzyme is an early viral protein.
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PMID:Epstein-Barr virus-specific DNA polymerase in virus-nonproducer Raji cells. 300 79

Epstein-Barr virus (EBV) has been found to be associated with nasopharyngeal carcinoma (NPC), and antibodies with high frequency and titer to EBV proteins have been found in sera from NPC patients. Raji cells, an EBV genome-carrying nonproducer cell line, treated with 12-O-tetradecanoylphorbol-13-acetate and n-butyrate induced a unique EBV DNA polymerase which has properties similar to the EBV DNA polymerase induced by 12-O-tetradecanoylphorbol-13-acetate in P3HR-1 cells, an EBV producer cell line. The possible presence of antibodies to this EBV DNA polymerase in NPC patient serum was examined. The mean number of EBV DNA polymerase units neutralized was 380 +/- 168 units/ml serum (mean +/- SD) in 48 sera from patients with NPC, whereas that in the sera from 52 healthy donors was 62 +/- 56 units/ml (p less than 0.01). The EBV DNA polymerase antibody was found to be associated with the immunoglobulin G but not the immunoglobulin A fraction, and its titer was not correlated with the titers against EBV DNase or virus capsid antigen-immunoglobulin A. Whether the EBV DNA polymerase antibody is against the EBV DNA polymerase core protein or its stimulating protein is still being investigated. This study demonstrated the high frequency and high titer of antibody against EBV DNA polymerase in serum from NPC patients and suggested the potential of utilizing this antibody titer to complement other methods for the early diagnosis or prognosis of NPC.
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PMID:Demonstration of Epstein-Barr virus-specific DNA polymerase in chemically induced Raji cells and its antibody in serum from patients with nasopharyngeal carcinoma. 301 19


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