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. 1987 Feb;84(3):871–875. doi: 10.1073/pnas.84.3.871

Immortality of cell cultures derived from brains of mice and hamsters infected with Creutzfeldt-Jakob disease agent.

E E Manuelidis, W W Fritch, J H Kim, L Manuelidis
PMCID: PMC304318  PMID: 3543937

Abstract

Isolates from six patients with Creutzfeldt-Jakob disease (CJD) were injected into various strains of hamsters and mice, and the infective agent was propagated. Serially passaged cultures were established from these CJD agent-infected brains and from uninfected control brains. All healthy cultures (21 out of 21) from CJD agent-infected brains became immortal and/or transformed. In contrast only 3 out of 13 normal brain cultures became immortal, and the rest died out with serial propagation in vitro. The fact that permanent cell lines were readily derived from multiple rodent strains and all CJD isolates tested suggests that a transforming capability is an intrinsic property of CJD agents. This conclusion is supported by demonstrations of in vitro cell transformation by CJD infectious brain fractions. Although the molecular mechanism of transformation events associated with the CJD agent is not presently known, a provocative possibility is that the CJD agent has a direct effect on the host genome by mechanisms analogous to those known for slowly oncogenic retroviruses.

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Selected References

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

  1. Buening G. M., Gustafson D. P. Growth characteristics of scrapie agent-infected mouse brain cell cultures. Am J Vet Res. 1971 Jun;32(6):953–958. [PubMed] [Google Scholar]
  2. Caspary E. A., Bell T. M. Growth potential of scrapie mouse brain in vitro. Nature. 1971 Jan 22;229(5282):269–270. doi: 10.1038/229269a0. [DOI] [PubMed] [Google Scholar]
  3. Clarke M. C., Haig D. A. Evidence for the multiplication of scrapie agent in cell culture. Nature. 1970 Jan 3;225(5227):100–101. doi: 10.1038/225100a0. [DOI] [PubMed] [Google Scholar]
  4. Clarke M. C., Haig D. A. Multiplication of scrapie agent in cell culture. Res Vet Sci. 1970 Sep;11(5):500–501. [PubMed] [Google Scholar]
  5. FIELD E. J., WINDSOR G. D. CULTURAL CHARACTERS OF SCRAPIE MOUSE BRAIN. Res Vet Sci. 1965 Jan;6:130–132. [PubMed] [Google Scholar]
  6. Freeman A. E., Kelloff G. J., Vernon M. L., Lane W. T., Capps W. I., Bumgarner S. D., Turner H. C., Huebner R. J. Prevalence of endogenous type-C virus in normal hamster tissues and hamster tumors induced by chemical carcinogens, simian virus 40, and polyoma virus. J Natl Cancer Inst. 1974 May;52(5):1469–1476. doi: 10.1093/jnci/52.5.1469. [DOI] [PubMed] [Google Scholar]
  7. Gajdusek D. C., Gibbs C. J., Alpers M. Experimental transmission of a Kuru-like syndrome to chimpanzees. Nature. 1966 Feb 19;209(5025):794–796. doi: 10.1038/209794a0. [DOI] [PubMed] [Google Scholar]
  8. Gajdusek D. C., Gibbs C. J., Jr, Rogers N. G., Basnight M., Hooks J. Persistence of viruses of kuru and Creutzfeldt-Jakob disease in tissue cultures of brain cells. Nature. 1972 Jan 14;235(5333):104–105. doi: 10.1038/235104a0. [DOI] [PubMed] [Google Scholar]
  9. Gibbs C. J., Jr, Gajdusek D. C., Asher D. M., Alpers M. P., Beck E., Daniel P. M., Matthews W. B. Creutzfeldt-Jakob disease (spongiform encephalopathy): transmission to the chimpanzee. Science. 1968 Jul 26;161(3839):388–389. doi: 10.1126/science.161.3839.388. [DOI] [PubMed] [Google Scholar]
  10. Haig D. A., Clarke M. C. Multiplication of the scrapie agent. Nature. 1971 Nov 12;234(5324):106–107. doi: 10.1038/234106a0. [DOI] [PubMed] [Google Scholar]
  11. Haig D. A., Pattison I. H. In-vitro growth of pieces of brain from scrapie-affected mice. J Pathol Bacteriol. 1967 Apr;93(2):724–727. doi: 10.1002/path.1700930243. [DOI] [PubMed] [Google Scholar]
  12. Hooks J., Gibbs C. J., Jr, Chopra H., Lewis M., Gajdusek D. C. Spontaneous tranformation of human brain cells grown in vitro and description of associated viurs particles. Science. 1972 Jun 30;176(4042):1420–1422. doi: 10.1126/science.176.4042.1420. [DOI] [PubMed] [Google Scholar]
  13. Katz M., Koprowski H., Moorhead P. S. Transformation of cell cultures derived from human brains. Science. 1973 Mar 9;179(4077):1019–1020. doi: 10.1126/science.179.4077.1019. [DOI] [PubMed] [Google Scholar]
  14. MANUELIDIS E. E. LONG-TERM LINES OF TISSUE CULTURES OF INTRACRANIAL TUMORS. J Neurosurg. 1965 Apr;22:368–373. doi: 10.3171/jns.1965.22.4.0368. [DOI] [PubMed] [Google Scholar]
  15. Manuelidis E. E. Creutzfeldt-Jakob disease. J Neuropathol Exp Neurol. 1985 Jan;44(1):1–17. doi: 10.1097/00005072-198501000-00001. [DOI] [PubMed] [Google Scholar]
  16. Masters C. L., Gajdusek D. C., Gibbs C. J., Jr Creutzfeldt-Jakob disease virus isolations from the Gerstmann-Sträussler syndrome with an analysis of the various forms of amyloid plaque deposition in the virus-induced spongiform encephalopathies. Brain. 1981 Sep;104(3):559–588. doi: 10.1093/brain/104.3.559. [DOI] [PubMed] [Google Scholar]
  17. Oleszak E. L., Manuelidis L., Manuelidis E. E. In vitro transformation elicited by Creutzfeldt-Jakob-infected brain material. J Neuropathol Exp Neurol. 1986 Sep;45(5):489–502. doi: 10.1097/00005072-198609000-00001. [DOI] [PubMed] [Google Scholar]
  18. Slack P. M., Dayan A. D., Slavin G., Tyrrell D. A. Morphological and virological investigations of cell strains cultured from the brain in Jakob-Creutzfeldt disease and subacute sclerosing panencephalitis. Br J Exp Pathol. 1975 Aug;56(4):377–387. [PMC free article] [PubMed] [Google Scholar]
  19. Yanagihara R. T., Asher D. M., Gibbs C. J., Jr, Gajdusek D. C. Attempts to establish cell cultures infected with the viruses of subacute spongiform encephalopathies. Proc Soc Exp Biol Med. 1980 Nov;165(2):298–305. doi: 10.3181/00379727-165-40974. [DOI] [PubMed] [Google Scholar]

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