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. 1962 Aug 1;116(2):141–157. doi: 10.1084/jem.116.2.141

SYNTHESIS OF VIRUS-SPECIFIC POLYMERS IN ADENOVIRUS-INFECTED CELLS: EFFECT OF 5-FLUORODEOXYURIDINE

John F Flanagan 1, Harold S Ginsberg 1
PMCID: PMC2137384  PMID: 13893423

Abstract

Biochemical synthesis in adenovirus-infected HeLa cells was studied utilizing 5-fluorodeoxyuridine (5-FUDR), a potent inhibitor of deoxyribonucleic acid production. Synthesis of saline-soluble DNA and infectious virus was completely suppressed by addition of the analogue to cells as late as 10 hours after infection. The inhibitory effect of this compound was totally reversed by addition of 10–6 M thymidine to the culture medium. Synthesis of DNA essential for virus production began 10 hours after infection and was completed by 16 hours after infection. These data support the hypothesis that the saline-soluble DNA is a precursor of infectious virus particles. Studies of antigen production indicated that formation of virus-specific proteins was directly dependent upon synthesis of DNA.

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Selected References

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  1. BOYER G. S., DENNY F. W., Jr, GINSBERG H. S. Sequential cellular changes produced by types 5 and 7 adenoviruses in HeLa cells and in human amniotic cells; cytological studies aided by fluorescein-labelled antibody. J Exp Med. 1959 Nov 1;110:827–844. doi: 10.1084/jem.110.5.827. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. BOYER G. S., LEUCHTENBERGER C., GINSBERG H. S. Cytological and cytochemical studies of HeLa cells infected with adeno-viruses. J Exp Med. 1957 Mar 1;105(3):195–216. doi: 10.1084/jem.105.3.195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. BURTON K. A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J. 1956 Feb;62(2):315–323. doi: 10.1042/bj0620315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. COLTER J. S., BIRD H. H., BROWN R. A. Infectivity of ribonucleic acid from Ehrlich ascites tumour cells infected with Mengo encephalitis. Nature. 1957 Apr 27;179(4565):859–860. doi: 10.1038/179859a0. [DOI] [PubMed] [Google Scholar]
  5. COLTER J. S., BIRD H. H., MOYER A. W., BROWN R. A. Infectivity of ribonucleic acid isolated from virus-infected tissues. Virology. 1957 Dec;4(3):522–532. doi: 10.1016/0042-6822(57)90084-3. [DOI] [PubMed] [Google Scholar]
  6. Cohen S. S., Flaks J. G., Barner H. D., Loeb M. R., Lichtenstein J. THE MODE OF ACTION OF 5-FLUOROURACIL AND ITS DERIVATIVES. Proc Natl Acad Sci U S A. 1958 Oct 15;44(10):1004–1012. doi: 10.1073/pnas.44.10.1004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. DISCHE Z. Qualitative and quantitative colorimetric determination of heptoses. J Biol Chem. 1953 Oct;204(2):983–997. [PubMed] [Google Scholar]
  8. Dimayorca G. A., Eddy B. E., Stewart S. E., Hunter W. S., Friend C., Bendich A. ISOLATION OF INFECTIOUS DEOXYRIBONUCLEIC ACID FROM SE POLYOMA-INFECTED TISSUE CULTURES. Proc Natl Acad Sci U S A. 1959 Dec;45(12):1805–1808. doi: 10.1073/pnas.45.12.1805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. EVERETT S. F., GINSBERG H. S. A toxin-like material separable from type 5 adenovirus particles. Virology. 1958 Dec;6(3):770–771. doi: 10.1016/0042-6822(58)90123-5. [DOI] [PubMed] [Google Scholar]
  10. GIERER A., SCHRAMM G. Infectivity of ribonucleic acid from tobacco mosaic virus. Nature. 1956 Apr 14;177(4511):702–703. doi: 10.1038/177702a0. [DOI] [PubMed] [Google Scholar]
  11. GINSBERG H. S., BADGER G. F., DINGLE J. H., JORDAN W. S., Jr, KATZ S. Etiologic relationship of the RI-67 agent to acute respiratory disease (ARD). J Clin Invest. 1955 Jun;34(6):820–831. doi: 10.1172/JCI103137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. GINSBERG H. S. Characteristics on the adenoviruses. III. Reproductive cycle of types 1 to 4. J Exp Med. 1958 Jan 1;107(1):133–152. doi: 10.1084/jem.107.1.133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. GINSBERG H. S., DIXON M. K. Deoxyribonucleic acid (DNA) and protein alterations in HeLa cells infected with type 4 adenovirus. J Exp Med. 1959 Apr 1;109(4):407–422. doi: 10.1084/jem.109.4.407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. GINSBERG H. S., DIXON M. K. Nucleuc acid synthesis in types 4 and 5 adenovirus-infected HeLa cells. J Exp Med. 1961 Feb 1;113:283–299. doi: 10.1084/jem.113.2.283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. GINSBERG H. S., GOLD E., JORDAN W. S., Jr Tryptose phosphate broth as supplementary factor for maintenance of HeLa cell tissue cultures. Proc Soc Exp Biol Med. 1955 May;89(1):66–71. doi: 10.3181/00379727-89-21718. [DOI] [PubMed] [Google Scholar]
  16. GREEN M. Biochemical studies on adenovirus multiplication. 1. Stimulation of phosphorus incorporation into deoxyribonucleic acid and ribouncleic acid. Virology. 1959 Nov;9:343–358. doi: 10.1016/0042-6822(59)90127-8. [DOI] [PubMed] [Google Scholar]
  17. GREEN M., DAESCH G. E. Biochemical studies on adenovirus multiplication. II. Kinetics of nucleic acid and protein synthesis in suspension cultures. Virology. 1961 Feb;13:169–176. doi: 10.1016/0042-6822(61)90051-4. [DOI] [PubMed] [Google Scholar]
  18. HAMLIN A., HARFORD C. G., PARKER E., VAN RAVENSWAAY T. Electron microscopy of HeLa cells infected with adenoviruses. J Exp Med. 1956 Sep 1;104(3):443–454. doi: 10.1084/jem.104.3.443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. ITO Y. A tumor-producing factor extracted by phenol from papillomatous tissue (Shope) of cottontail rabbits. Virology. 1960 Dec;12:596–601. doi: 10.1016/0042-6822(60)90182-3. [DOI] [PubMed] [Google Scholar]
  20. KLEMPERER H. G., PEREIRA H. G. Study of adenovirus antigens fractionated by chromatography on DEAE-cellulose. Virology. 1959 Dec;9:536–545. doi: 10.1016/0042-6822(59)90147-3. [DOI] [PubMed] [Google Scholar]
  21. LAGERMALM G., KJELLEN L., THORSSON K. G., SVEDMYR A. Electron microscopy of HeLa cells infected with agents of the adenovirus (APC-RI-ARD) group. Arch Gesamte Virusforsch. 1957;7(3):221–241. doi: 10.1007/BF01240877. [DOI] [PubMed] [Google Scholar]
  22. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  23. PEREIRA H. G. A protein factor responsible for the early cytopathic effect of adenoviruses. Virology. 1958 Dec;6(3):601–611. doi: 10.1016/0042-6822(58)90109-0. [DOI] [PubMed] [Google Scholar]
  24. SALZMAN N. P. The rate of formation of vaccinia deoxyribonucleic acid and vaccinia virus. Virology. 1960 Jan;10:150–152. doi: 10.1016/0042-6822(60)90015-5. [DOI] [PubMed] [Google Scholar]
  25. WATANABE I. The effect of ultraviolet light on the production of bacterial virus protein. J Gen Physiol. 1957 Mar 20;40(4):521–531. doi: 10.1085/jgp.40.4.521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. WILCOX W. C., GINSBERG H. S. Purification and immunological characterization of types 4 and 5 adenovirus-soluble antigens. Proc Natl Acad Sci U S A. 1961 Apr 15;47:512–526. doi: 10.1073/pnas.47.4.512. [DOI] [PMC free article] [PubMed] [Google Scholar]

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