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. 1964 Nov 30;120(6):1099–1115. doi: 10.1084/jem.120.6.1099

ENDOSYMBIOTIC RELATIONSHIP BETWEEN ANIMAL VIRUSES AND HOST CELLS

A STUDY OF RABIES VIRUS IN TISSUE CULTURE

Mario V Fernandes 1, Tadeusz J Wiktor 1, Hilary Koprowski 1
PMCID: PMC2137788  PMID: 14238928

Abstract

RE cultures infected with a fixed rabies virus were studied. The virus can propagate itself in these cells for an indefinite period of time without interfering with cell growth. The present study characterizes this truly endosymbiotic relationship. Virus-specific antigen was detected in the cytoplasm of each cell by fluorescein-labeled antirabies serum but only 4 to 5 per cent of the cells released infectious virus. All cells undergoing division showed viral antigen throughout the mitotic process. Also, the growth rate, plating efficiency, and morphological characteristics of both the infected and control cultures were identical. No difference was detected between the RE and the RE-CVS cell populations by RNA and DNA labeling experiments, using H3-thymidine, and H3-uridine. Although antirabies serum effectively inhibited the spread of extracellular virus, it did not interfere with cell-to-cell transmission of the virus during mitosis, in the course of 9 cell transfers during 53 days. RE-CVS cells, when exposed to fresh antirabies serum, lysed completely but inactivated serum had no lytic effect. The addition of fresh hamster complement to the inactivated serum restored its cytolytic properties. The serially passaged RE-CVS virus gradually became less virulent for mice and displayed a weak antigenicity in the mouse protection test. Another feature of the RE-CVS cell system is its resistance to infection with homologous and heterologous viruses despite the apparent absence of an interferon-like substance.

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Selected References

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

  1. COONS A. H., KAPLAN M. H. Localization of antigen in tissue cells; improvements in a method for the detection of antigen by means of fluorescent antibody. J Exp Med. 1950 Jan 1;91(1):1–13. doi: 10.1084/jem.91.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. EAGLE H. The minimum vitamin requirements of the L and HeLa cells in tissue culture, the production of specific vitamin deficiencies, and their cure. J Exp Med. 1955 Nov 1;102(5):595–600. doi: 10.1084/jem.102.5.595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. FERNANDES M. V., WIKTOR T. J., KOPROWSKI H. MECHANISM OF THE CYTOPATHIC EFFECT OF RABIES VIRUS IN TISSUE CULTURE. Virology. 1963 Sep;21:128–131. doi: 10.1016/0042-6822(63)90312-x. [DOI] [PubMed] [Google Scholar]
  4. GOLDWASSER R. A., KISSLING R. E., CARSKI T. R., HOSTY T. S. Fluorescent antibody staining of rabies virus antigens in the salivary glands of rabid animals. Bull World Health Organ. 1959;20:579–588. [PMC free article] [PubMed] [Google Scholar]
  5. HARE J. D., BALDUZZI P., MORGAN H. R. Polyoma virus and L cell relationship. I. Some characteristics of a cell line persistently infected with polyoma virus. J Natl Cancer Inst. 1963 Jan;30:45–56. [PubMed] [Google Scholar]
  6. LOVE R., FERNANDES M. V., KOPROWSKI H. CYTOCHEMISTRY OF INCLUSION BODIES IN TISSUE CULTURE CELLS INFECTED WITH RABIES VIRUS. Proc Soc Exp Biol Med. 1964 Jul;116:560–563. doi: 10.3181/00379727-116-29306. [DOI] [PubMed] [Google Scholar]
  7. MACPHERSON I., STOKER M. Polyoma transformation of hamster cell clones--an investigation of genetic factors affecting cell competence. Virology. 1962 Feb;16:147–151. doi: 10.1016/0042-6822(62)90290-8. [DOI] [PubMed] [Google Scholar]
  8. POMERAT C. M., SLICK W. C. Isolation and growth of endothelial cells in tissue culture. Nature. 1963 Jun 1;198:859–861. doi: 10.1038/198859a0. [DOI] [PubMed] [Google Scholar]
  9. PUCK T. T., MARCUS P. I., CIECIURA S. J. Clonal growth of mammalian cells in vitro; growth characteristics of colonies from single HeLa cells with and without a feeder layer. J Exp Med. 1956 Feb 1;103(2):273–283. doi: 10.1084/jem.103.2.273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. ROIZMAN B., SCHLUEDERBERG A. E. Virus infection of cells in mitosis. III. Cytology of mitotic and amitotic HEp-2 cells infected with measles virus. J Natl Cancer Inst. 1962 Jan;28:35–53. [PubMed] [Google Scholar]
  11. RUBIN H., TEMIN H. M. Infection with the Rous sarcoma virus in vitro. Fed Proc. 1958 Dec;17(4):994–1003. [PubMed] [Google Scholar]
  12. SAKSELA E., MOORHEAD P. S. Enhancement of secondary constrictions and the heterochromatic X in human cells. Cytogenetics. 1962;1:225–244. doi: 10.1159/000129733. [DOI] [PubMed] [Google Scholar]
  13. SPENDLOVE R. S., LENNETTE E. H., JOHN A. C. THE ROLE OF THE MITOTIC APPARATUS IN THE INTRACELLULAR LOCATION OF REOVIRUS ANTIGEN. J Immunol. 1963 Apr;90:554–560. [PubMed] [Google Scholar]
  14. WALKER D. L., HINZE H. C. A carrier state of mumps virus in human conjunctiva cells. I. General characteristics. J Exp Med. 1962 Nov 1;116:739–750. doi: 10.1084/jem.116.5.739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. WALKER D. L., HINZE H. C. A carrier state of mumps virus in human conjunctiva cells. II. Observations on intercellular transfer of virus and virus release. J Exp Med. 1962 Nov 1;116:751–758. doi: 10.1084/jem.116.5.751. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. WHEELOCK E. F., TAMM I. Mitosis and division in HeLa cells infected with influenza or Newcastle disease virus. Virology. 1959 Aug;8:532–536. doi: 10.1016/0042-6822(59)90056-x. [DOI] [PubMed] [Google Scholar]

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