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. 1972 Sep;69(9):2589–2593. doi: 10.1073/pnas.69.9.2589

Sequence of Spontaneous Epstein-Barr Virus Activation and Selective DNA Synthesis in Activated Cells in the Presence of Hydroxyurea

Berge Hampar *, Jeffery G Derge †, Lidia M Martos †, Malle A Tagamets †, Mary Alice Burroughs *
PMCID: PMC426995  PMID: 4341700

Abstract

The sequence of spontaneous Epstein-Barr virus activation was studied in P3HR-1 carrier cells and in P3HR-1(BrdU) cells made resistant to 5-bromodeoxyuridine. Virus activation was initiated during the normal cell cycle, and recruitment of additional virus-activated cells was prevented by the DNA inhibitors, 1-β-D-arabinofuranosylcytosine and hydroxyurea. Virus activation was followed by synthesis of the early antigen complex in the absence of additional detectable DNA synthesis. Early antigen synthesis was followed by hydroxyurea-resistant synthesis of new DNA, which in the case of P3HR-1(BrdU) cells was characterized by the appearance of thymidine kinase. The newly synthesized DNA banded in neutral cesium chloride at peaks corresponding to normal human DNA and Epstein-Barr viral DNA. Synthesis of viral antigen was seen only in cells that had undergone hydroxyurea-resistant DNA synthesis.

Keywords: 5-bromodeoxyuridine, early antigen, viral antigen, thymidine kinase

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Gerber P. Activation of Epstein-Barr virus by 5-bromodeoxyuridine in "virus-free" human cells (complement-fixing antigen-immunofluorescence-leukocytes). Proc Natl Acad Sci U S A. 1972 Jan;69(1):83–85. doi: 10.1073/pnas.69.1.83. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Gergely L., Klein G., Ernberg I. The action of DNA antagonists on Epstein-Barr virus (EBV)-associated early antigen (EA) in Burkitt lymphoma lines. Int J Cancer. 1971 Mar 15;7(2):293–302. doi: 10.1002/ijc.2910070214. [DOI] [PubMed] [Google Scholar]
  3. Glaser R., O'Neill F. J. Hybridization of Burkitt lymphoblastoid cells. Science. 1972 Jun 16;176(4040):1245–1247. doi: 10.1126/science.176.4040.1245. [DOI] [PubMed] [Google Scholar]
  4. Hampar B., Derge J. G., Martos L. M., Walker J. L. Persistence of a repressed Epstein-Barr virus genome in Burkitt lymphoma cells made resistant to 5-bromodeoxyuridine. Proc Natl Acad Sci U S A. 1971 Dec;68(12):3185–3189. doi: 10.1073/pnas.68.12.3185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hampar B., Derge J. G., Martos L. M., Walker J. L. Synthesis of Epstein-Barr virus after activation of the viral genome in a "virus-negative" human lymphoblastoid cell (Raji) made resistant to 5-bromodeoxyuridine (thymidine kinase-virus antigen-immunofluorescence-herpesvirus fingerprints). Proc Natl Acad Sci U S A. 1972 Jan;69(1):78–82. doi: 10.1073/pnas.69.1.78. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hampar B., Gerber P., Hsu K. C., Martos L. M., Walker J. L., Sigüenza R. F., Wells G. A. Immunoferritin and immunofluorescent studies with Epstein-Barr virus and herpes simplex virus by use of human sera and hyperimmune rabbit sera. J Natl Cancer Inst. 1970 Jul;45(1):75–85. [PubMed] [Google Scholar]
  7. Hampar B., Martos L. M., Walker J. L. Epstein-Barr virus in human lymphoblastoid cells: enhancing the percentage of virus-positive cells by cocultivation with African green monkey (Vero) cells. J Natl Cancer Inst. 1971 Sep;47(3):535–537. [PubMed] [Google Scholar]
  8. Henle G., Henle W. Immunofluorescence in cells derived from Burkitt's lymphoma. J Bacteriol. 1966 Mar;91(3):1248–1256. doi: 10.1128/jb.91.3.1248-1256.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Henle W., Henle G., Zajac B. A., Pearson G., Waubke R., Scriba M. Differential reactivity of human serums with early antigens induced by Epstein-Barr virus. Science. 1970 Jul 10;169(3941):188–190. doi: 10.1126/science.169.3941.188. [DOI] [PubMed] [Google Scholar]
  10. Lieberman M. W., Sell S., Farber E. Deoxyribonucleoside incorporation and the role of hydroxyurea in a model lymphocyte system for studying DNA repair in carcinogenesis. Cancer Res. 1971 Sep;31(9):1307–1312. [PubMed] [Google Scholar]
  11. Nii S., Rosenkranz H. S., Morgan C., Rose H. M. Electron microscopy of herpes simplex virus. 3. Effect of hydroxyurea. J Virol. 1968 Oct;2(10):1163–1171. doi: 10.1128/jvi.2.10.1163-1171.1968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Nonoyama M., Pagano J. S. Detection of Epstein-Barr viral genome in nonproductive cells. Nat New Biol. 1971 Sep 22;233(38):103–106. doi: 10.1038/newbio233103a0. [DOI] [PubMed] [Google Scholar]
  13. Warner H. R., Hobbs M. D. Effect of hydroxyurea on replication of bacteriophage T4 in Escherichia coli. J Virol. 1969 Mar;3(3):331–336. doi: 10.1128/jvi.3.3.331-336.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. YOUNG C. W., HODAS S. HYDROXYUREA: INHIBITORY EFFECT ON DNA METABOLISM. Science. 1964 Nov 27;146(3648):1172–1174. doi: 10.1126/science.146.3648.1172. [DOI] [PubMed] [Google Scholar]
  15. Zur Hausen H., Schulte-Holthausen H. Presence of EB virus nucleic acid homology in a "virus-free" line of Burkitt tumour cells. Nature. 1970 Jul 18;227(5255):245–248. doi: 10.1038/227245a0. [DOI] [PubMed] [Google Scholar]

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