Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1990 Oct;87(20):7963–7967. doi: 10.1073/pnas.87.20.7963

A monoclonal antibody that neutralizes Epstein-Barr virus, human cytomegalovirus, human herpesvirus 6, and bacteriophage T4 DNA polymerases.

C H Tsai 1, M V Williams 1, R Glaser 1
PMCID: PMC54872  PMID: 1700422

Abstract

A monoclonal antibody (mAb) designated 55H3 was produced by using chemically induced Epstein-Barr virus genome-positive B95-8 cells. mAb 55H3, which reacted with an 85- to 80-kDa polypeptide, neutralized Epstein-Barr virus-encoded DNA polymerase activity in crude extracts of chemically induced M-ABA, HR-1, and B95-8 cells, as well as the partially purified Epstein-Barr virus DNA polymerase in a dose-dependent manner. The mAb also neutralized the virus-encoded DNA polymerase activity from cells infected with human cytomegalovirus, human herpesvirus 6, and the purified bacteriophage T4 DNA polymerases. However, mAb 55H3 did not neutralize the DNA polymerase activities encoded for by herpes simplex virus types 1 and 2, the reverse transcriptase of avian myeloblastosis virus, or Escherichia coli DNA polymerase 1 (Klenow fragment). These results suggest that mAb 55H3 recognizes an epitope common to some herpesviruses and T4 DNA polymerases and further supports the hypothesis that these organisms are evolutionarily related.

Full text

PDF
7963

Images in this article

Selected References

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

  1. Baer R., Bankier A. T., Biggin M. D., Deininger P. L., Farrell P. J., Gibson T. J., Hatfull G., Hudson G. S., Satchwell S. C., Séguin C. DNA sequence and expression of the B95-8 Epstein-Barr virus genome. Nature. 1984 Jul 19;310(5974):207–211. doi: 10.1038/310207a0. [DOI] [PubMed] [Google Scholar]
  2. Bernad A., Zaballos A., Salas M., Blanco L. Structural and functional relationships between prokaryotic and eukaryotic DNA polymerases. EMBO J. 1987 Dec 20;6(13):4219–4225. doi: 10.1002/j.1460-2075.1987.tb02770.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cheng Y. C., Chen J. Y., Glaser R., Henle W. Frequency and levels of antibodies to Epstein-Barr virus-specific DNase are elevated in patients with nasopharyngeal carcinoma. Proc Natl Acad Sci U S A. 1980 Oct;77(10):6162–6165. doi: 10.1073/pnas.77.10.6162. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chiou J. F., Li J. K., Cheng Y. C. Demonstration of a stimulatory protein for virus-specified DNA polymerase in phorbol ester-treated Epstein-Barr virus-carrying cells. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5728–5731. doi: 10.1073/pnas.82.17.5728. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Davison A. J., Scott J. E. The complete DNA sequence of varicella-zoster virus. J Gen Virol. 1986 Sep;67(Pt 9):1759–1816. doi: 10.1099/0022-1317-67-9-1759. [DOI] [PubMed] [Google Scholar]
  6. Earl P. L., Jones E. V., Moss B. Homology between DNA polymerases of poxviruses, herpesviruses, and adenoviruses: nucleotide sequence of the vaccinia virus DNA polymerase gene. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3659–3663. doi: 10.1073/pnas.83.11.3659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gallo M. L., Dorsky D. I., Crumpacker C. S., Parris D. S. The essential 65-kilodalton DNA-binding protein of herpes simplex virus stimulates the virus-encoded DNA polymerase. J Virol. 1989 Dec;63(12):5023–5029. doi: 10.1128/jvi.63.12.5023-5029.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gibbs J. S., Chiou H. C., Hall J. D., Mount D. W., Retondo M. J., Weller S. K., Coen D. M. Sequence and mapping analyses of the herpes simplex virus DNA polymerase gene predict a C-terminal substrate binding domain. Proc Natl Acad Sci U S A. 1985 Dec;82(23):7969–7973. doi: 10.1073/pnas.82.23.7969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Goodman S. R., Prezyna C., Benz W. C. Two Epstein-Barr virus-associated DNA polymerase activities. J Biol Chem. 1978 Dec 10;253(23):8617–8628. [PubMed] [Google Scholar]
  10. Henle G., Henle W., Klein G. Demonstration of two distinct components in the early antigen complex of Epstein-Barr virus-infected cells. Int J Cancer. 1971 Sep 15;8(2):272–282. doi: 10.1002/ijc.2910080212. [DOI] [PubMed] [Google Scholar]
  11. Henle G., Henle W., Klein G., Gunven P., Clifford P., Morrow R. H., Ziegler J. L. Antibodies to early Epstein-Barr virus-induced antigens in Burkitt's lymphoma. J Natl Cancer Inst. 1971 Apr;46(4):861–871. [PubMed] [Google Scholar]
  12. Henle W., Henle G., Gunvén P., Klein G., Clifford P., Singh S. Patterns of antibodies to Epstein-Barr virus-induced early antigens in Burkitt's lymphoma. Comparison of dying patients with long-term survivors. J Natl Cancer Inst. 1973 May;50(5):1163–1173. doi: 10.1093/jnci/50.5.1163. [DOI] [PubMed] [Google Scholar]
  13. Henle W., Ho H. C., Henle G., Kwan H. C. Antibodies to Epstein-Barr virus-related antigens in nasopharyngeal carcinoma. Comparison of active cases with long-term survivors. J Natl Cancer Inst. 1973 Aug;51(2):361–369. [PubMed] [Google Scholar]
  14. Kallin B., Sternås L., Saemundssen A. K., Luka J., Jörnvall H., Eriksson B., Tao P. Z., Nilsson M. T., Klein G. Purification of Epstein-Barr virus DNA polymerase from P3HR-1 cells. J Virol. 1985 May;54(2):561–568. doi: 10.1128/jvi.54.2.561-568.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kieff E., Dambaugh T., Heller M., King W., Cheung A., van Santen V., Hummel M., Beisel C., Fennewald S., Hennessy K. The biology and chemistry of Epstein-Barr virus. J Infect Dis. 1982 Oct;146(4):506–517. doi: 10.1093/infdis/146.4.506. [DOI] [PubMed] [Google Scholar]
  16. Knopf C. W., Weisshart K. The herpes simplex virus DNA polymerase: analysis of the functional domains. Biochim Biophys Acta. 1988 Dec 20;951(2-3):298–314. doi: 10.1016/0167-4781(88)90100-5. [DOI] [PubMed] [Google Scholar]
  17. Kouzarides T., Bankier A. T., Satchwell S. C., Weston K., Tomlinson P., Barrell B. G. Sequence and transcription analysis of the human cytomegalovirus DNA polymerase gene. J Virol. 1987 Jan;61(1):125–133. doi: 10.1128/jvi.61.1.125-133.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  19. Larder B. A., Kemp S. D., Darby G. Related functional domains in virus DNA polymerases. EMBO J. 1987 Jan;6(1):169–175. doi: 10.1002/j.1460-2075.1987.tb04735.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Li J. S., Zhou B. S., Dutschman G. E., Grill S. P., Tan R. S., Cheng Y. C. Association of Epstein-Barr virus early antigen diffuse component and virus-specified DNA polymerase activity. J Virol. 1987 Sep;61(9):2947–2949. doi: 10.1128/jvi.61.9.2947-2949.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Miller R. L., Glaser R., Rapp F. Studies of an Epstein-Barr virus-induced DNA polymerase. Virology. 1977 Feb;76(2):494–502. doi: 10.1016/0042-6822(77)90232-x. [DOI] [PubMed] [Google Scholar]
  22. Moss B., Cooper N. Genetic evidence for vaccinia virus-encoded DNA polymerase: isolation of phosphonoacetate-resistant enzyme from the cytoplasm of cells infected with mutant virus. J Virol. 1982 Aug;43(2):673–678. doi: 10.1128/jvi.43.2.673-678.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Nagata K., Guggenheimer R. A., Hurwitz J. Specific binding of a cellular DNA replication protein to the origin of replication of adenovirus DNA. Proc Natl Acad Sci U S A. 1983 Oct;80(20):6177–6181. doi: 10.1073/pnas.80.20.6177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Nonoyama M., Huang C. H., Pagano J. S., Klein G., Singh S. DNA of Epstein-Barr virus detected in tissue of Burkitt's lymphoma and nasopharyngeal carcinoma. Proc Natl Acad Sci U S A. 1973 Nov;70(11):3265–3268. doi: 10.1073/pnas.70.11.3265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Petit R. G., Leung K., Shaw J. E. Specific immune serum to the Epstein-Barr virus DNA polymerase. J Virol. 1987 Oct;61(10):3331–3334. doi: 10.1128/jvi.61.10.3331-3334.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Quinn J. P., McGeoch D. J. DNA sequence of the region in the genome of herpes simplex virus type 1 containing the genes for DNA polymerase and the major DNA binding protein. Nucleic Acids Res. 1985 Nov 25;13(22):8143–8163. doi: 10.1093/nar/13.22.8143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Spicer E. K., Rush J., Fung C., Reha-Krantz L. J., Karam J. D., Konigsberg W. H. Primary structure of T4 DNA polymerase. Evolutionary relatedness to eucaryotic and other procaryotic DNA polymerases. J Biol Chem. 1988 Jun 5;263(16):7478–7486. [PubMed] [Google Scholar]
  28. Tan R. S., Li J. S., Grill S. P., Nutter L. M., Cheng Y. C. Demonstration of Epstein-Barr virus-specific DNA polymerase in chemically induced Raji cells and its antibody in serum from patients with nasopharyngeal carcinoma. Cancer Res. 1986 Oct;46(10):5024–5028. [PubMed] [Google Scholar]
  29. Tarr K. L., Glaser R. Predilection of a nasopharyngeal carcinoma-derived isolate of Epstein-Barr virus for infection of specific subsets of B lymphocytes. J Med Virol. 1989 Sep;29(1):47–52. doi: 10.1002/jmv.1890290109. [DOI] [PubMed] [Google Scholar]
  30. Tsai C. H., Williams M. V., Glaser R. A monoclonal antibody that neutralizes Epstein-Barr virus DNA polymerase activity. Intervirology. 1990;31(2-4):215–222. doi: 10.1159/000150156. [DOI] [PubMed] [Google Scholar]
  31. Tunón P., Johansson K. E. Yet another improved silver staining method for the detection of proteins in polyacrylamide gels. J Biochem Biophys Methods. 1984 May;9(2):171–179. doi: 10.1016/0165-022x(84)90008-3. [DOI] [PubMed] [Google Scholar]
  32. Waldman W. J., Sneddon J. M., Stephens R. E., Roberts W. H. Enhanced endothelial cytopathogenicity induced by a cytomegalovirus strain propagated in endothelial cells. J Med Virol. 1989 Aug;28(4):223–230. doi: 10.1002/jmv.1890280405. [DOI] [PubMed] [Google Scholar]
  33. Wang T. S., Wong S. W., Korn D. Human DNA polymerase alpha: predicted functional domains and relationships with viral DNA polymerases. FASEB J. 1989 Jan;3(1):14–21. doi: 10.1096/fasebj.3.1.2642867. [DOI] [PubMed] [Google Scholar]
  34. Williams M. V., Ablashi D. V., Salahuddin S. Z., Glaser R. Demonstration of the human herpesvirus 6-induced DNA polymerase and DNase. Virology. 1989 Nov;173(1):223–230. doi: 10.1016/0042-6822(89)90238-9. [DOI] [PubMed] [Google Scholar]
  35. Wong S. W., Wahl A. F., Yuan P. M., Arai N., Pearson B. E., Arai K., Korn D., Hunkapiller M. W., Wang T. S. Human DNA polymerase alpha gene expression is cell proliferation dependent and its primary structure is similar to both prokaryotic and eukaryotic replicative DNA polymerases. EMBO J. 1988 Jan;7(1):37–47. doi: 10.1002/j.1460-2075.1988.tb02781.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. zur Hausen H., Schulte-Holthausen H., Klein G., Henle W., Henle G., Clifford P., Santesson L. EBV DNA in biopsies of Burkitt tumours and anaplastic carcinomas of the nasopharynx. Nature. 1970 Dec 12;228(5276):1056–1058. doi: 10.1038/2281056a0. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES