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. 1966 Sep 1;124(3):501–520. doi: 10.1084/jem.124.3.501

ON THE ROLE OF THE RESPONSE OF THE CELL MEMBRANE IN DETERMINING VIRUS VIRULENCE

CONTRASTING EFFECTS OF THE PARAINFLUENZA VIRUS SV5 IN TWO CELL TYPES

Kathryn V Holmes 1, Purnell W Choppin 1
PMCID: PMC2138234  PMID: 4288512

Abstract

The simian myxovirus SV5 multiplies in a continuous line of baby hamster kidney (BHK21-F) cells causing extensive cell fusion, followed by cell death. After inoculation of 15 PFU/cell, the latent period was 7 hr, the doubling time approximately 60 min, and the yield 7 PFU per cell. Giant cell formation began about 6 hr after infection and rapidly progressed to the formation by 14 to 18 hr of a single syncytium which disintegrated by 24 to 36 hr. In contrast, SV5 multiplies in primary rhesus monkey kidney cells for long periods of time producing high yields of virus with little cytopathic effect. High multiplicities of SV5 induced cell fusion in BHK21-F cells within 1 hr in the absence of virus multiplication but had no visible effect on monkey kidney cells. Time-lapse photomicrography has demonstrated that giant cells form by fusion of infected cells, and that some polykaryocytes divide. During aberrant division of polykaryocytes giant nuclei are formed from the nuclear material of several parent nuclei. The cytoplasmic development of viral antigens as demonstrated by immunofluorescence is similar in BHK21-F and monkey kidney cells. Synthesis of cellular DNA, RNA, and protein in monkey kidney cells is not shut off by SV5-infection, and in BHK21-F cells synthesis of these macromolecules is not inhibited until after extensive cell fusion has occurred 12 to 15 hr after infection. Persistently infected BHK21-F and monkey kidney cells have been serially carried through 11 and 28 cell passages, respectively. The results suggest that whether SV5 acts as a moderate virus, as in monkey kidney cells, or a virulent virus, as in BHK21-F cells, depends on the response of the cell membrane to the virus.

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Selected References

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  1. AOYAMA Y. Changes of cultured cells infected with measles virus. Jpn J Exp Med. 1959 Oct;29:535–545. [PubMed] [Google Scholar]
  2. Atherton J. G., Chaparas S. D., Cremer M., Gordon I. Mechanism of Polykaryocytosis Associated with Noncytopathic Infection by Measles Virus. J Bacteriol. 1965 Jul;90(1):213–219. doi: 10.1128/jb.90.1.213-219.1965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. BABLANIAN R., EGGERS H. J., TAMM I. STUDIES ON THE MECHANISM OF POLIOVIRUS-INDUCED CELL DAMAGE. I. THE RELATION BETWEEN POLIOVIRUS,-INDUCED METABOLIC AND MORPHOLOGICAL ALTERATIONS IN CULTURED CELLS. Virology. 1965 May;26:100–113. doi: 10.1016/0042-6822(65)90030-9. [DOI] [PubMed] [Google Scholar]
  4. BUNGAY C., WATKINS J. F. OBSERVATIONS ON POLYKARYOCYTOSIS IN HELA CELLS INFECTED WITH HERPES SIMPLEX VIRUS. Br J Exp Pathol. 1964 Feb;45:48–55. [PMC free article] [PubMed] [Google Scholar]
  5. CASCARDO M. R., KARZON D. T. MEASLES VIRUS GIANT CELL INDUCING FACTOR (FUSION FACTOR). Virology. 1965 Jun;26:311–325. doi: 10.1016/0042-6822(65)90279-5. [DOI] [PubMed] [Google Scholar]
  6. CHOPPIN P. W. MULTIPLICATION OF A MYXOVIRUS (SV5) WITH MINIMAL CYTOPATHIC EFFECTS AND WITHOUT INTERFERENCE. Virology. 1964 Jun;23:224–233. doi: 10.1016/0042-6822(64)90286-7. [DOI] [PubMed] [Google Scholar]
  7. CHOPPIN P. W., PHILIPSON L. The inactivation of enterovirus infectivity by the sulfhydryl reagent p-chloromercuribenzoate. J Exp Med. 1961 Apr 1;113:713–734. doi: 10.1084/jem.113.4.713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. CHOPPIN P. W., STOECKENIUS W. THE MORPHOLOGY OF SV5 VIRUS. Virology. 1964 Jun;23:195–202. doi: 10.1016/0042-6822(64)90282-x. [DOI] [PubMed] [Google Scholar]
  9. Chang P. W., Hsiung G. D. Experimental infection of parainfluenza virus type 5 in mice, hamsters and monkeys. J Immunol. 1965 Oct;95(4):591–601. [PubMed] [Google Scholar]
  10. Choppin P. W. Effect of actinomycin D and halogenated deoxyuridines on the replication of simian virus 5. Proc Soc Exp Biol Med. 1965 Dec;120(3):699–702. doi: 10.3181/00379727-120-30629. [DOI] [PubMed] [Google Scholar]
  11. DARNELL J. E., Jr Early events in poliovirus infection. Cold Spring Harb Symp Quant Biol. 1962;27:149–158. doi: 10.1101/sqb.1962.027.001.017. [DOI] [PubMed] [Google Scholar]
  12. DULBECCO R. CHARACTERISTICS OF VIRUS-CELL COMPLEXES. Am J Med. 1965 May;38:669–677. doi: 10.1016/0002-9343(65)90189-0. [DOI] [PubMed] [Google Scholar]
  13. DULBECCO R., VOGT M. Plaque formation and isolation of pure lines with poliomyelitis viruses. J Exp Med. 1954 Feb;99(2):167–182. doi: 10.1084/jem.99.2.167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. EAGLE H. Amino acid metabolism in mammalian cell cultures. Science. 1959 Aug 21;130(3373):432–437. doi: 10.1126/science.130.3373.432. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. FRANKLIN R. M., BALTIMORE D. Patterns of macromolecular synthesis in normal and virus-infected mammalian cells. Cold Spring Harb Symp Quant Biol. 1962;27:175–198. doi: 10.1101/sqb.1962.027.001.019. [DOI] [PubMed] [Google Scholar]
  17. GOLDBERG I. H., RABINOWITZ M. Actionmycin D inhibition of deoxyribonucleic acid-dependent synthesis of ribonucleic acid. Science. 1962 Apr 27;136(3513):315–316. doi: 10.1126/science.136.3513.315. [DOI] [PubMed] [Google Scholar]
  18. HENLE G., DEINHARDT F., GIRARDI A. Cytolytic effects of mumps virus in tissue cultures of epithelial cells. Proc Soc Exp Biol Med. 1954 Nov;87(2):386–393. doi: 10.3181/00379727-87-21390. [DOI] [PubMed] [Google Scholar]
  19. HOWES D. W., MELNICK J. L., REISSIG M. Sequence of morphological changes in epithelial cell cultures infected with poliovirus. J Exp Med. 1956 Sep 1;104(3):289–304. doi: 10.1084/jem.104.3.289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. HO Y. D. Investigations into syncytium formation in cultures of stable cell lines infected with parainfluenza I virus. II. Morphology of syncytium formation in tissue cultures and a hypothesis concerning its mechanism. Acta Virol. 1962 May;6:202–206. [PubMed] [Google Scholar]
  21. HSIUNG G. D., ISACSON P., McCOLLUM R. W. Studies of a myxovirus isolated from human blood. I. Isolation and properties. J Immunol. 1962 Mar;88:284–290. [PubMed] [Google Scholar]
  22. HULL R. N., MINNER J. R., SMITH J. W. New viral agents recovered from tissue cultures of monkey kidney cells. I. Origin and properties of cytopathogenic agents S.V.1, S.V.2, S.V.4, S.V.5, S.V.6, S.V.11, S.V.12 and S.V.15. Am J Hyg. 1956 Mar;63(2):204–215. doi: 10.1093/oxfordjournals.aje.a119804. [DOI] [PubMed] [Google Scholar]
  23. Harris H. Behaviour of differentiated nuclei in heterokaryons of animal cells from different species. Nature. 1965 May 8;206(984):583–588. doi: 10.1038/206583a0. [DOI] [PubMed] [Google Scholar]
  24. ISHIDA N., HOMMA M., OSATO T., HINUMA Y., MIYAMOTO T. PERSISTENT INFECTION IN HELA CELLS WITH HEMADSORPTION VIRUS TYPE 2. Virology. 1964 Dec;24:670–672. doi: 10.1016/0042-6822(64)90224-7. [DOI] [PubMed] [Google Scholar]
  25. KOHN A. POLYKARYOCYTOSIS INDUCED BY NEWCASTLE DISEASE VIRUS IN MONOLAYERS OF ANIMAL CELLS. Virology. 1965 Jun;26:228–245. doi: 10.1016/0042-6822(65)90050-4. [DOI] [PubMed] [Google Scholar]
  26. LEPINE P., CHANY C., DROZ B., ROBBE-FOSSAT F. Cytopathogenic effect of two newly recognized myxovirus strains: mechanism of syncytial formation. Ann N Y Acad Sci. 1959 Jul 21;81:62–72. doi: 10.1111/j.1749-6632.1959.tb49295.x. [DOI] [PubMed] [Google Scholar]
  27. LOVE R., SUSKIND R. G. Cytopathology of parainfluenza, type 3, virus infection in HeLa and monkey kidney cells in vitro. Exp Cell Res. 1961 Sep;24:521–526. doi: 10.1016/0014-4827(61)90451-7. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. NII S., KAMAHORA J. Cytopathic changes induced by herpes simplex virus. Biken J. 1961 Dec;4:255–270. [PubMed] [Google Scholar]
  30. OKADA Y., TADOKORO J. Analysis of giant polynuclear cell formation caused by HVJ virus from Ehrlich's ascites tumor cells. II. Quantitative analysis of giant polynuclear cell formation. Exp Cell Res. 1962 Feb;26:108–118. doi: 10.1016/0014-4827(62)90206-9. [DOI] [PubMed] [Google Scholar]
  31. OKADA Y., TADOKORO J. THE DISTRIBUTION OF CELL FUSION CAPACITY AMONG SEVERAL CELL STRAINS OR CELLS CAUSED BY HVJ. Exp Cell Res. 1963 Dec;32:417–430. doi: 10.1016/0014-4827(63)90182-4. [DOI] [PubMed] [Google Scholar]
  32. OKADA Y., YAMADA K., TADOKORO J. EFFECT OF ANTISERUM ON THE CELL FUSION REACTION CAUSED BY HVJ. Virology. 1964 Mar;22:397–409. doi: 10.1016/0042-6822(64)90030-3. [DOI] [PubMed] [Google Scholar]
  33. REBEL G., FONTANGES R., COLOBERT L. [The lipid nature of substances responsible for the hemolytic activity of Myxo-virus paraninfluenzae I (Sendai virus)]. Ann Inst Pasteur (Paris) 1962 Feb;102:137–152. [PubMed] [Google Scholar]
  34. REDA I. M., ROTT R., SCHAEFER W. FLUORESCENT ANTIBODY STUDIES WITH NDV-INFECTED CELL SYSTEMS. Virology. 1964 Mar;22:422–425. doi: 10.1016/0042-6822(64)90033-9. [DOI] [PubMed] [Google Scholar]
  35. REICH E., FRANKLIN R. M., SHATKIN A. J., TATUM E. L. Effect of actinomycin D on cellular nucleic acid synthesis and virus production. Science. 1961 Aug 25;134(3478):556–557. doi: 10.1126/science.134.3478.556. [DOI] [PubMed] [Google Scholar]
  36. ROIZMAN B. Polykaryocytosis induced by viruses. Proc Natl Acad Sci U S A. 1962 Feb;48:228–234. doi: 10.1073/pnas.48.2.228. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. ROIZMAN B. Polykaryocytosis. Cold Spring Harb Symp Quant Biol. 1962;27:327–342. doi: 10.1101/sqb.1962.027.001.031. [DOI] [PubMed] [Google Scholar]
  38. 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]
  39. RUSTIGIAN R. A carrier state in HeLa cells with measles virus (Edmonston strain) apparently associated with non-infectious virus. Virology. 1962 Jan;16:101–104. doi: 10.1016/0042-6822(62)90212-x. [DOI] [PubMed] [Google Scholar]
  40. SCHULTZ E. W., HABEL K. SA virus; a new member of the myxovirus group. J Immunol. 1959 Mar;82(3):274–278. [PubMed] [Google Scholar]
  41. SYKES J. A., MOORE E. B. A simple tissue culture chamber. Tex Rep Biol Med. 1960;18:288–297. [PubMed] [Google Scholar]
  42. 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]
  43. WARREN J., JENSEN K., MASON R. The syncytial viruses. Ann N Y Acad Sci. 1962 Nov 30;101:520–526. doi: 10.1111/j.1749-6632.1962.tb18893.x. [DOI] [PubMed] [Google Scholar]
  44. WATERSON A. P. Two kinds of myxovirus. Nature. 1962 Mar 24;193:1163–1164. doi: 10.1038/1931163a0. [DOI] [PubMed] [Google Scholar]
  45. WHEELOCK E. F., TAMM I. Biochemical basis for alterations in structure and function of HeLa cells infected with Newcastle disease virus. J Exp Med. 1961 Nov 1;114:617–632. doi: 10.1084/jem.114.5.617. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. WHEELOCK E. F., TAMM I. Effect of multiplicity of infection on Newcastle disease virus-HeLa cell interaction. J Exp Med. 1961 Feb 1;113:317–338. doi: 10.1084/jem.113.2.317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. 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]
  48. ZHDANOV V. M., BUKRINSKAYA A. G. Studies on the initial stage of virus-cell interaction. Acta Virol. 1962 Mar;6:105–113. [PubMed] [Google Scholar]

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