Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1997 Dec;71(12):9333–9342. doi: 10.1128/jvi.71.12.9333-9342.1997

Isolation of highly fusogenic variants of simian virus 5 from persistently infected cells that produce and respond to interferon.

D F Young 1, L Didcock 1, R E Randall 1
PMCID: PMC230236  PMID: 9371592

Abstract

A series of experiments were undertaken to examine how interferon and neutralizing antibodies influence the ability of simian virus 5 (SV5) (strain W3) to establish and maintain persistent infections in murine cells. In contrast to the rapid decline in SV5 protein synthesis observed in murine BALB/c fibroblasts (BF cells), which produce and respond to interferon, between 24 and 48 h postinfection there was no inhibition of virus protein synthesis in MSFI- cells, skin fibroblasts derived from alpha/beta-interferon receptor knockout BALB/c mice. Furthermore, the addition of anti-interferon antibodies to the culture medium of infected BF cells significantly reduced the observed decline in virus protein synthesis. Following infection of untreated BF cells, the majority replicated virus but survived the infection and eventually cleared the virus after 8 to 15 days. However, not all the cells were cured, and the cultures became persistently infected. Upon passage of persistently infected cultures, the virus fluxed between active and repressed states as a consequence of interferon production. This resulted in a balance being reached in which only 5 to 20% of the cells were infected at any one time. After 30 passages of the persistently infected cells, highly fusogenic virus variants arose (one of which was isolated and termed W3-f). W3-f remained as sensitive to interferon as the parental W3 isolate but, in the absence of interferon, spread much more rapidly than the parental W3 strain through BF cell monolayers. Sequence analysis revealed no deduced amino acid differences between the F proteins of W3 and W3-f. BF cell cultures persistently infected with W3-f were rapidly cleared of virus by the addition of virus-neutralizing antibodies to the culture medium. In contrast, neutralizing antibodies had little effect on the numbers of cells persistently infected with W3 over several passages. These results suggest that the ability of paramyxoviruses to cause cell-cell fusion may be selected for in vivo as a consequence of their adaptation to the interferon response rather than their need to escape from neutralizing antibodies. The significance of these observations with regard to persistent parainfluenza virus infections in vivo is further discussed.

Full Text

The Full Text of this article is available as a PDF (3.6 MB).

Selected References

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

  1. 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]
  2. Delage G., Brochu P., Pelletier M., Jasmin G., Lapointe N. Giant-cell pneumonia caused by parainfluenza virus. J Pediatr. 1979 Mar;94(3):426–429. doi: 10.1016/s0022-3476(79)80591-0. [DOI] [PubMed] [Google Scholar]
  3. Fearns R., Young D. F., Randall R. E. Evidence that the paramyxovirus simian virus 5 can establish quiescent infections by remaining inactive in cytoplasmic inclusion bodies. J Gen Virol. 1994 Dec;75(Pt 12):3525–3539. doi: 10.1099/0022-1317-75-12-3525. [DOI] [PubMed] [Google Scholar]
  4. Fishaut M., Tubergen D., McIntosh K. Cellular response to respiratory viruses with particular reference to children with disorders of cell-mediated immunity. J Pediatr. 1980 Feb;96(2):179–186. doi: 10.1016/s0022-3476(80)80799-2. [DOI] [PubMed] [Google Scholar]
  5. Frank A. L., Taber L. H., Wells C. R., Wells J. M., Glezen W. P., Paredes A. Patterns of shedding of myxoviruses and paramyxoviruses in children. J Infect Dis. 1981 Nov;144(5):433–441. doi: 10.1093/infdis/144.5.433. [DOI] [PubMed] [Google Scholar]
  6. Fujinami R. S., Oldstone M. B. Alterations in expression of measles virus polypeptides by antibody: molecular events in antibody-induced antigenic modulation. J Immunol. 1980 Jul;125(1):78–85. [PubMed] [Google Scholar]
  7. Fujinami R. S., Oldstone M. B. Antiviral antibody reacting on the plasma membrane alters measles virus expression inside the cell. Nature. 1979 Jun 7;279(5713):529–530. doi: 10.1038/279529a0. [DOI] [PubMed] [Google Scholar]
  8. Gross P. A., Green R. H., Curnen M. G. Persistent infection with parainfluenza type 3 virus in man. Am Rev Respir Dis. 1973 Oct;108(4):894–898. doi: 10.1164/arrd.1973.108.4.894. [DOI] [PubMed] [Google Scholar]
  9. Hanada N., Morishima T., Nishikawa K., Isomura S., Nagai Y. Interferon-mediated self-limiting growth of respiratory syncytial virus in mouse embryo cells. J Med Virol. 1986 Dec;20(4):363–370. doi: 10.1002/jmv.1890200409. [DOI] [PubMed] [Google Scholar]
  10. Ito Y., Tsurudome M., Hishiyama M. Effects of antibodies and interferon on mumps virus persistently infected L929 cells. Generation of variant viruses in the cells during incubation with monoclonal antibodies and interferon. Arch Virol. 1986;88(3-4):217–230. doi: 10.1007/BF01310876. [DOI] [PubMed] [Google Scholar]
  11. Jacobson S., McFarland H. F. Measles virus persistence in human lymphocytes: a role for virus-induced interferon. J Gen Virol. 1982 Dec;63(2):351–357. doi: 10.1099/0022-1317-63-2-351. [DOI] [PubMed] [Google Scholar]
  12. Jarvis W. R., Middleton P. J., Gelfand E. W. Parainfluenza pneumonia in severe combined immunodeficiency disease. J Pediatr. 1979 Mar;94(3):423–425. doi: 10.1016/s0022-3476(79)80590-9. [DOI] [PubMed] [Google Scholar]
  13. Karp D., Willis J., Wilfert C. M. Parainfluenza virus II and the immunocompromised host. Am J Dis Child. 1974 Apr;127(4):592–593. doi: 10.1001/archpedi.1974.02110230138025. [DOI] [PubMed] [Google Scholar]
  14. Kessler S. W. Rapid isolation of antigens from cells with a staphylococcal protein A-antibody adsorbent: parameters of the interaction of antibody-antigen complexes with protein A. J Immunol. 1975 Dec;115(6):1617–1624. [PubMed] [Google Scholar]
  15. Muchmore H. G., Parkinson A. J., Humphries J. E., Scott E. N., McIntosh D. A., Scott L. V., Cooney M. K., Miles J. A. Persistent parainfluenza virus shedding during isolation at the South Pole. Nature. 1981 Jan 15;289(5794):187–189. doi: 10.1038/289187a0. [DOI] [PubMed] [Google Scholar]
  16. Müller U., Steinhoff U., Reis L. F., Hemmi S., Pavlovic J., Zinkernagel R. M., Aguet M. Functional role of type I and type II interferons in antiviral defense. Science. 1994 Jun 24;264(5167):1918–1921. doi: 10.1126/science.8009221. [DOI] [PubMed] [Google Scholar]
  17. Nagai Y., Ito Y., Hamaguchi M., Yoshida T., Matsumoto T. Relation of interferon production to the limited replication of Newcastle disease virus in L cells. J Gen Virol. 1981 Jul;55(Pt 1):109–116. doi: 10.1099/0022-1317-55-1-109. [DOI] [PubMed] [Google Scholar]
  18. Paterson R. G., Harris T. J., Lamb R. A. Fusion protein of the paramyxovirus simian virus 5: nucleotide sequence of mRNA predicts a highly hydrophobic glycoprotein. Proc Natl Acad Sci U S A. 1984 Nov;81(21):6706–6710. doi: 10.1073/pnas.81.21.6706. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Randall R. E., Dinwoodie N. Intranuclear localization of herpes simplex virus immediate-early and delayed-early proteins: evidence that ICP 4 is associated with progeny virus DNA. J Gen Virol. 1986 Oct;67(Pt 10):2163–2177. doi: 10.1099/0022-1317-67-10-2163. [DOI] [PubMed] [Google Scholar]
  20. Randall R. E., Young D. F., Goswami K. K., Russell W. C. Isolation and characterization of monoclonal antibodies to simian virus 5 and their use in revealing antigenic differences between human, canine and simian isolates. J Gen Virol. 1987 Nov;68(Pt 11):2769–2780. doi: 10.1099/0022-1317-68-11-2769. [DOI] [PubMed] [Google Scholar]
  21. Rehberg E., Kelder B., Hoal E. G., Pestka S. Specific molecular activities of recombinant and hybrid leukocyte interferons. J Biol Chem. 1982 Oct 10;257(19):11497–11502. [PubMed] [Google Scholar]
  22. WALKER D. L. THE VIRAL CARRIER STATE IN ANIMAL CELL CULTURES. Prog Med Virol. 1964;6:111–148. [PubMed] [Google Scholar]
  23. Yamada A., Tsurudome M., Hishiyama M., Ito Y. Abortive infection of mumps virus in murine cell lines. J Gen Virol. 1984 May;65(Pt 5):973–980. doi: 10.1099/0022-1317-65-5-973. [DOI] [PubMed] [Google Scholar]
  24. van den Broek M. F., Müller U., Huang S., Aguet M., Zinkernagel R. M. Antiviral defense in mice lacking both alpha/beta and gamma interferon receptors. J Virol. 1995 Aug;69(8):4792–4796. doi: 10.1128/jvi.69.8.4792-4796.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES