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. 1961 Jan 31;113(2):317–338. doi: 10.1084/jem.113.2.317

EFFECT OF MULTIPLICITY OF INFECTION ON NEWCASTLE DISEASE VIRUS-HELA CELL INTERACTION

E Frederick Wheelock 1, Igor Tamm 1
PMCID: PMC2137359  PMID: 13784768

Abstract

The effects of a hundred-fold difference in virus/cell multiplicity on the interaction of Newcastle disease virus (NDV) with HeLa cells were studied, and various phases of the virus reproductive cycle were related to cellular consequences of infection. At both multiplicities used all cells were infected. The following events occurred 1 to 2 hours earlier in cells which were inoculated with the higher multiplicity: (a) first appearance of newly made virus antigen, and the amount present at any time during the period of rapid increase; (b) onset and time course of production of infective virus; (c) development by infected cells of hemadsorbing ability; (d) onset and time course of inhibition of mitosis; and (e) onset and time course of marked cell damage. Double infection of HeLa cells with NDV and NWS was demonstrated by the fluorescent antibody technique, and was used to show that the establishment of interference against NWS was also dependent upon the multiplicity of NDV. In cells inoculated at each multiplicity, newly made virus antigen appeared at the same time as the first infective virus particles. Infective virus rapidly reached a peak, and then declined. Viral antigen continued to increase for several hours after the decline in infective virus had begun. Thus, only a small fraction of the virus antigen produced was incorporated into new infective particles. The maximal yield of such particles was only 6 to 11 per HeLa cell. Over 95 per cent of new virus was cell-associated, but could be neutralized by treatment with antiserum before disruption of cells. Mitosis occurred in cells which had produced and released infective NDV. Progressive inhibition of mitotic activity in infected cells was correlated with continued production of viral antigen. Marked cytopathic changes developed after mitotic activity had decreased to low levels. The mechanism by which NDV inhibits mitosis in HeLa cells is discussed.

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Selected References

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  1. BURNSTEIN T., BANG F. B. Infection of the upper respiratory tract of the chick with a mild (vaccine) strain of Newcastle disease virus. II. Studies on the pathogenesis of the infection. Bull Johns Hopkins Hosp. 1958 Mar;102(3):135–157. [PubMed] [Google Scholar]
  2. CHANOCK R. M. Cytopathogenic effect of Newcastle virus in monkey kidney cultures and interference with poliomyelitis viruses. Proc Soc Exp Biol Med. 1955 Jul;89(3):379–381. doi: 10.3181/00379727-89-21816. [DOI] [PubMed] [Google Scholar]
  3. COOPER P. D. Shortened latency' as a result of multiple infection by vesicular stomatitis virus in chick cell culture. J Gen Microbiol. 1958 Oct;19(2):340–349. doi: 10.1099/00221287-19-2-340. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. EAGLE H. The specific amino acid requirements of a human carcinoma cell (Stain HeLa) in tissue culture. J Exp Med. 1955 Jul 1;102(1):37–48. doi: 10.1084/jem.102.1.37. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. FOGH J. Latent period in monkey kidney and HeLa cell monolayer cultures infected with poliomyelitis virus. Proc Soc Exp Biol Med. 1955 Jul;89(3):494–497. doi: 10.3181/00379727-89-21857. [DOI] [PubMed] [Google Scholar]
  7. FOGH J. Relation between multiplicity of exposure, adsorption, and cytopathogenic effect of poliomyelitis virus in monkey kidney tissue cultures. Virology. 1955 Sep;1(3):324–333. doi: 10.1016/0042-6822(55)90028-3. [DOI] [PubMed] [Google Scholar]
  8. GRANOFF A. Noninfectious forms of Newcastle disease and influenza viruses; studies on noninfectious virus occurring within cells that are producing fully infectious virus. Virology. 1955 Dec;1(5):516–532. doi: 10.1016/0042-6822(55)90040-4. [DOI] [PubMed] [Google Scholar]
  9. HENLE G., GIRARDI A., HENLE W. A non-transmissible cytopathogenic effect of influenza virus in tissue culture accompanied by formation of non-infectious hemagglutinins. J Exp Med. 1955 Jan 1;101(1):25–41. doi: 10.1084/jem.101.1.25. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. KAPLAN A. S. A study of the herpes simplex virus-rabbit kidney cell system by the plaque technique. Virology. 1957 Dec;4(3):435–457. doi: 10.1016/0042-6822(57)90078-8. [DOI] [PubMed] [Google Scholar]
  11. MARCUS P. I., PUCK T. T. Host-cell interaction of animal viruses. I. Titration of cell-killing by viruses. Virology. 1958 Oct;6(2):405–423. doi: 10.1016/0042-6822(58)90091-6. [DOI] [PubMed] [Google Scholar]
  12. PAINTER R. B., DREW R. M. Studies on deoxyribonucleic acid metabolism in human cancer cell cultures (HeLa). I. The temporal relationships of deoxyribonucleic acid synthesis to mitosis and turnover time. Lab Invest. 1959 Jan-Feb;8(1):278–285. [PubMed] [Google Scholar]
  13. PRINCE A. M., GINSBERG H. S. Immunohistochemical studies on the interaction between Ehrlich ascites tumor cells and Newcastle disease virus. J Exp Med. 1957 Feb 1;105(2):177–188. doi: 10.1084/jem.105.2.177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. RUBIN H., FRANKLIN R. M., BALUDA M. Infection and growth of Newcastle disease virus (NDV) in cultures of chick embryo lung epithelium. Virology. 1957 Jun;3(3):587–600. doi: 10.1016/0042-6822(57)90012-0. [DOI] [PubMed] [Google Scholar]
  15. SHELOKOV A., VOGEL J. E., CHI L. Hemadsorption (adsorption-hemagglutination) test for viral agents in tissue culture with special reference to influenza. Proc Soc Exp Biol Med. 1958 Apr;97(4):802–809. doi: 10.3181/00379727-97-23884. [DOI] [PubMed] [Google Scholar]
  16. STOKER M. G., NEWTON A. The effect of herpes virus on HeLa cells dividing parasynchronously. Virology. 1959 Apr;7(4):438–448. doi: 10.1016/0042-6822(59)90072-8. [DOI] [PubMed] [Google Scholar]
  17. TEMIN H. M., RUBIN H. A kinetic study of infection of chick embryo cells in vitro by Rous sarcoma virus. Virology. 1959 Jun;8(2):209–222. doi: 10.1016/0042-6822(59)90005-4. [DOI] [PubMed] [Google Scholar]
  18. TRAVER M. I., NORTHROP R. L., WALKER D. L. Site of intracellular antigen production by myxoviruses. Proc Soc Exp Biol Med. 1960 Jun;104:268–273. doi: 10.3181/00379727-104-25803. [DOI] [PubMed] [Google Scholar]
  19. TYRRELL D. A. J., HORSFALL F. L., Jr A procedure which eliminates nonspecific inhibitor from human serum but does not affect specific antibodies against influenza viruses. J Immunol. 1952 Nov;69(5):563–574. [PubMed] [Google Scholar]
  20. Vogt M., Dulbecco R. VIRUS-CELL INTERACTION WITH A TUMOR-PRODUCING VIRUS. Proc Natl Acad Sci U S A. 1960 Mar;46(3):365–370. doi: 10.1073/pnas.46.3.365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. WHEELOCK E. F., TAMM I. Enumeration of cell-infecting particles of Newcastle disease virus by the fluorescent antibody technique. J Exp Med. 1961 Feb 1;113:301–316. doi: 10.1084/jem.113.2.301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. YOUNGNER J. S. Monolayer tissue cultures. III. Propagation of poliomyelitis viruses in cultures of trypsin-dispersed monkey kidney cells. J Immunol. 1954 Dec;73(6):392–396. [PubMed] [Google Scholar]

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