Inhibition of DNA Polymerase from Herpes Simplex Virus-Infected Wi-38 Cells by Phosphonoacetic Acid

Mao, James C.-H.; Robishaw, Ellen E.; Overby, L. R.

doi:10.1128/jvi.15.5.1281-1283.1975

Cited by 174 publications

(52 citation statements)

References 11 publications

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“…As ACV and PAA inhibit only the productive replication of EBV, they may have similar mechanisms of action, even though these two antiviral compounds are structurally dissimilar. It will be interesting to determine whether ACV or its phosphorylated derivatives inhibit EBV DNA replication by binding to a virus-specific DNA polymerase, as has been suggested for the mechanism of action of PAA in the herpes simplex virus (HSV) system (20), or whether it inhibits EBV DNA synthesis by chain termination. ACV, an acyclic nucleoside analog of guanosine, is phosphorylated in HSV-infected cells to mono-, di-, and triphosphates (4).…”

Section: Discussionmentioning

confidence: 99%

Effect of acyclovir [9-(2-hydroxyethoxymethyl)guanine] on Epstein-Barr virus DNA replication

Colby¹,

Shaw²,

Elion³

et al. 1980

J Virol

203

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The effect of acyclovir [9-(2-hydroxyethoxymethyl)guanine] on Epstein-Barr virus (EBV) DNA replication in the lymphoblastoid cell lines P3HR-1 and Raji is reported. Acyclovir at a concentration of 100 microM completely inhibited EBV DNA synthesis in superinfected Raji cells, but did not inhibit DNA synthesis in mock-infected cells. The number of EBV genome equivalents per cell in the virus-producing cell line P3HR-1 was significantly reduced by acyclovir, whereas the number of latent EBV genomes in Raji cells was not affected by the drug. In situ cytohybridization performed on untreated P3HR-1 cultures revealed the presence of relatively large amounts of EBV DNA in 15 to 20% of the cells. After a 100 microM drug treatment, no P3HR-1 cells contained levels of EBV DNA detectable by in situ cytohybridization. Indirect immunofluorescence studies demonstrated that during treatment with 100 microM acyclovir for 7 days, the percentage of P3HR-1 cells expressing viral capsid antigen was reduced. The EBV DNA remaining in P3HR-1 cells after treatment with 100 microM acyclovir (approximately 14 genomes per cell) had the properties of covalently closed circular DNA with an average molecular weight of 108 X 10(6), as determined by contour length measurements.

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Section: Discussionmentioning

confidence: 99%

Effect of acyclovir [9-(2-hydroxyethoxymethyl)guanine] on Epstein-Barr virus DNA replication

Colby¹,

Shaw²,

Elion³

et al. 1980

J Virol

203

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“…To determine the effect of DNA synthesis on the level of accumulation of 65KDBP compared with that of ICP8, we infected cells in the presence and absence of PAA, a specific inhibitor of the HSV DNA polymerase (19,24). Because MAb 39S readily detects only the native form of ICP8 and does not cross-react with other protein species (36; unpublished results), lysates of infected and mock-infected cells were applied directly to nitrocellulose and probed with either MAb 6898 or 39S to detect 65KDBP or ICP8, respectively.…”

Section: Methodsmentioning

confidence: 99%

Kinetics of expression of the gene encoding the 65-kilodalton DNA-binding protein of herpes simplex virus type 1

Goodrich

Rixon

Parris

1989

J Virol

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The 65-kilodalton DNA-binding protein (65KDBp) of herpes simplex virus type 1, encoded by gene UL42, is required for herpes simplex virus origin-dependent DNA replication (C. A. Wu, N. J. Nelson, D. J. McGeoch, and M. D. Challberg, J. Virol. 62:435-443, 1988). We found by indirect immunofluorescence with monoclonal antibody to 65KDBP that the protein was first detectable at 3 h postinfection. It localized first to the inner periphery of the nucleus, but accumulated in large globular compartments within the nucleus by 6 h postinfection in a pattern similar to that displayed by the major DNA-binding protein ICP8. Immune electron microscopy revealed that 65KDBP was associated with the marginated heterochromatin at the early times, but migrated further into the nucleus at late times when the only discernible areas devoid of 65KDBP were the nucleoli and heterochromatin. The 65KDBP gene is a member of the 0i kinetic class as determined by the ability of the mRNA to be expressed at significant levels even in the absence of viral DNA synthesis. Furthermore, in the presence or absence of the DNA polymerase inhibitor phosphonoacetic acid, the patterns of accumulation of protein as well as mRNA were virtually indistinguishable from those displayed by the model 0 genes encoding ICP8 and thymidine kinase. Nuclear run-on experiments demonstrated that maximum rates of

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“…Phosphonoacetate is a potent inhibitor of herpesvirus-induced DNA polymerase [Mao and Robishaw, 1975;Leinbach et al, 19761. HeLa DNA polymerase-a was reported to be equally sensitive [Bolden et al, 19751, but other DNA polymerases were not inhibited at low concentrations [Bolden et al, 1975;Mao et al, 1975;Leinbach, 19761. The soluble DNA polymerase was found to be relatively resistant to this compound.…”

Section: Effect Of Inhibitors On Sotuble Dna Polymerase From Hepatitimentioning

confidence: 99%

Properties of soluble dna polymerase from sera of hepatitis b virus carriers

Mao

Otis

Mushahwar

et al. 1980

Journal of Medical Virology

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A soluble DNA polymerase was purified 8,000-fold from hepatitis B surface antigen positive serum. The molecular weight of the enzyme by gel filtration was about 1.60 X 10(5), the sedimentation coefficient was 5.5S, the apparent Km for dTTP was 4 micrometer, the optimum pH in the presence of Mg2+ was 9.2, and the pl was 4.7. The enzyme was found in HBsAg-positive sera and required an external primer for activity. The properties of the DNA polymerase were different from hepatitis B virus particle enzyme and from vertebrate and bacterial DNA polymerases. The prevalence of this enzyme did not correlate with HBeAg or particle DNA polymerase in HBsAg-positive sera.

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Inhibition of DNA Polymerase from Herpes Simplex Virus-Infected Wi-38 Cells by Phosphonoacetic Acid

Cited by 174 publications

References 11 publications

Effect of acyclovir [9-(2-hydroxyethoxymethyl)guanine] on Epstein-Barr virus DNA replication

Effect of acyclovir [9-(2-hydroxyethoxymethyl)guanine] on Epstein-Barr virus DNA replication

Kinetics of expression of the gene encoding the 65-kilodalton DNA-binding protein of herpes simplex virus type 1

Properties of soluble dna polymerase from sera of hepatitis b virus carriers

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