1887

Abstract

SUMMARY

Infection of mouse L-2 fibroblasts with mouse hepatitis virus (MHV) results in strong inhibition of host cell protein synthesis. Since it has been suggested in other virus systems that translational control is modulated by changes in the intracellular ionic environment, we investigated the possible occurrence of similar changes during MHV infection. Membrane permeability to extracellular sodium ions was measured by culturing MHV-infected cells in the presence of Na. Sodium influx into MHV- infected cells rose dramatically from 4 to 6 h post-infection. This influx correlated chronologically with the expression of MHV-mediated cell fusion. Cell fusion was blocked by the addition of a monoclonal antibody against the MHV E glycoprotein. This addition also resulted in a reduction in the normal influx of Na, suggesting that E expression was responsible, directly or indirectly, for the increased permeability to sodium ions in infected cells. Cultures of MHV-infected cells were labelled with [S]methionine in the presence of medium supplemented with sodium chloride at final concentrations ranging from 150 m to 350 m. Incorporation of radiolabel into proteins decreased with increasing NaCl concentration; however, the ratio of viral to cellular protein synthesis remained relatively constant. Similarly, alteration of intracellular Na and K levels by treatment of infected cells with ouabain had little effect on the pattern of viral/cellular protein synthesis. Using monoclonal anti-Eantibody to inhibit Na influx, we demonstrated normal inhibition of host cell protein synthesis. We therefore conclude that MHV-induced shut-off of host translation is not mediated by changes in intracellular Na concentrations.

Keyword(s): cations , MHV and translation
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1987-08-01
2024-10-03
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References

  1. Benedetto A., Rossi G. B., Amici C., Belardelli F., Cioe L., Carruba G., Carrasco L. 1980; Inhibition of animal virus production by means of translational inhibitors unable to penetrate normal cells. Virology 106:123–132
    [Google Scholar]
  2. Cahn F., Lubin M. 1978; Inhibition of elongation steps of protein synthesis and reduced potassium concentrations in reticulocytes and reticulocyte lysate. Journal of Biological Chemistry 253:7798–7803
    [Google Scholar]
  3. Carrasco L. 1977; The inhibition of cell functions after viral infection. A proposed general mechanism. FEBS Letters 76:11–15
    [Google Scholar]
  4. Carrasco L., Smith A. E. 1976; Sodium ions and the shut off of host cell protein synthesis by picomaviruses. Nature; London: 264807–809
    [Google Scholar]
  5. Cheley S., Anderson R. 1981; Cellular synthesis and modification of murine hepatitis virus polypeptides. Journal of General Virology 54:301–311
    [Google Scholar]
  6. Cherney C. S., Wilhelm J. M. 1979; Differential translation in normal and adenovirus type 5-infected human cells and cell-free systems. Journal of Virology 30:533–542
    [Google Scholar]
  7. Christman J. K. 1973; Effect of elevated potassium level and amino acid deprivation on polysome distribution and a rate of protein synthesis in L cells. Biochimica et biophysica acta 294:138–152
    [Google Scholar]
  8. Collins A. R., Knobler R. l., Powell H., Buchmeier M. J. 1982; Monoclonal antibodies to murine hepatitis virus 4 (strain JHM) define the viral glycoprotein responsible for attachment and cell fusion. Virology 119:358–371
    [Google Scholar]
  9. Francoeur A. M. 1978; Evidence against the role of K+in the shut-off of protein synthesis by vesicular stomatitis virus. Journal of General Virology 39:551–554
    [Google Scholar]
  10. Garrahan P. J., Glynn I. M. 1967; The behaviour of the sodium pump in red cells in the absence of external potassium. Journal of Physiology 192:159–174
    [Google Scholar]
  11. Garry R. F., Bishop J. M., Parker S., Nostbrook R., Lewis G., Waite M. R. F. 1979; Na+ and K+concentrations and the regulation of protein synthesis in Sindbis virus-infected chick cells. Virology 96:108–120
    [Google Scholar]
  12. Garry R. F., Ulug E. t., Bose H. R. 1982; Membrane-mediated alterations of intracellular Na+and K+in lytic virus-infected and retrovirus-transformed cells. Bioscience Reports 2:617–623
    [Google Scholar]
  13. Glynn I. M. 1968; Membrane adenosine triphosphate and cation transport. British Medical Bulletin 24:165–169
    [Google Scholar]
  14. Hackstadt T., Mallavia I. P. 1982; Sodium and potassium transport in herpes simplex virus-infected cells. Journal of General Virology 60:199–207
    [Google Scholar]
  15. Haspel M. v., Lampert P. W., Oldstone M. B. A. 1978; Temperature-sensitive mutants of mouse hepatitis virus produce a high incidence of demyelination. Proceedings of the National Academy of Sciences U.S.A.: 754033–4036
    [Google Scholar]
  16. Hilton A., Mizzen L., Macintyre G., Cheley S., Anderson R. 1986; Translational control in murine hepatitis virus infection. Journal of General Virology 67:923–932
    [Google Scholar]
  17. Ledbetter M., Libin M. 1977; Control of protein synthesis in human fibroblasts by intracellular potassium. Experimental Cell Research 105:223–236
    [Google Scholar]
  18. Lubin M. 1967; Intracellular potassium and macromolecular synthesis in mammalian cells. Nature; London: 213:451–453
    [Google Scholar]
  19. Lucas A., Flintoff W., Anderson R., Percy D., Coulter M., Dales S. 1977; In vivo and in vitro models of demyelinating diseases: tropism of the JHM strain of murine hepatitis virus for cells of glial origin. Cell 12:553–560
    [Google Scholar]
  20. Lucas A., Coulter M., Anderson R., Dales S., Flintoff W. 1978; In vivo and in vitro models of demyelinating diseases. II. Persistence and host-regulated thermosensitivity in cells of neural derivation infected with mouse hepatitis and measles viruses. Virology 88:325–337
    [Google Scholar]
  21. Manaker R. A., Piczak C. v., Miller A. A., Stanton M. F. 1961; A hepatitis virus complicating studies with mouse leukemia. Journal of the National Cancer Institute 27:29–44
    [Google Scholar]
  22. Mizzen L., Cheley S., Rao M., Wolf R., Anderson R. 1983; Fusion resistance and decreased infectibility as major host cell determinants of coronavirus persistence. Virology 128:407–417
    [Google Scholar]
  23. Nagashima K., Wege H., Meyermann R., Ter Meulen V. 1978; Coronavirus induced subacute demyelinating encephalomyelitis in rats: a morphological analysis. Acta neuropathologica 44:63–70
    [Google Scholar]
  24. Nair C. N. 1981; Monovalent cation metabolism and cytopathic effects of poliovirus-infected HeLa cells. Journal of Virology 31:268–273
    [Google Scholar]
  25. Nair C. N. 1984; Na and K changes in animal virus-infected HeLa cells. Journal of General Virology 65:1135–1138
    [Google Scholar]
  26. Nuss D. L., Oppermann H., Koch G. 1975; Selective blockage of initiation of host protein synthesis in RNA- virus infected cells. Proceedings of the National Academy of Sciences U.S.A.: 721258–1262
    [Google Scholar]
  27. Oppermann H., Koch G. 1976; On the regulation of protein synthesis in vaccinia virus infected cells. Journal of General Virology 32:261–273
    [Google Scholar]
  28. Oppermann H., Saborio J. L., Azrucki T., Koch G. 1973; Sensitization of cells for viral RNA infection by inhibition of macromolecular synthesis. Federation Proceedings 32:1755
    [Google Scholar]
  29. Panet R., Atlan H. 1979; Coupling between K+ efflux, ATP metabolism and protein synthesis in reticulocytes. Biochemical and Biophysical Research Communications 8:619–626
    [Google Scholar]
  30. Robb J. A., Bond C. W. 1979; Pathogenic murine coronaviruses. III. Biological and biochemical characterization of temperature-sensitive mutants of JHMV. Virology 94:385–399
    [Google Scholar]
  31. Rothfels R. h., Axelrod A. A., Siminovitch L., Mcculloch E. A., Parker R. C. 1959; The origin of altered cell lines from mouse, monkey and man as indicated by chromosome and transplantation studies. Canadian Cancer Conference 3:189–214
    [Google Scholar]
  32. Saborio J. L., Pong S. S., Koch G. 1974; Selective and reversible inhibition of protein synthesis in mammalian cells. Journal of Molecular Biology 85:195–211
    [Google Scholar]
  33. Siddell S. G., Anderson R., Cavanagh D., Fujiwara K., Klenk H. D., Macnaughton M. R., Pensaert M., Stohlman S. A., Sturman L., Van Der Zeijst B. A. M. 1983; Coronaviridae. Intervirology 20:181–189
    [Google Scholar]
  34. Sorensen O., Percy D., Dales S. 1980; In vivo and in vitro models of demyelinating diseases. III. JHM virus infection of rats. Archives of Neurology 37:478–484
    [Google Scholar]
  35. Sorensen O., Coulter-Mackie M. B., Puchalski S., Dales S. 1984; In vivo and in vitro models of demyelinating disease. IX. Progression of JHM virus infection in the central nervous system of the rat during overt and asymptomatic phases. Virology 137:347–357
    [Google Scholar]
  36. Stohlman S. A., Weiner L. P. 1981; Chronic central nervous system demyelination in mice after JHM virus infection. Neurology 31:38–44
    [Google Scholar]
  37. Ulug E. T., Bose H. R. 1985; Effect of tunicamycin on the development of the cytopathic effect in Sindbis virus- infected avian fibroblasts. Virology 143:546–557
    [Google Scholar]
  38. Ulug E. T., Garry R. F., Waite M. R. F., Bose H. R. 1984; Alterations in monovalent cation transport in Sindbis virus-infected chick cells. Virology 132:118–130
    [Google Scholar]
  39. Weiner L. P., Johnson R. T., Harndon R. M. 1973; Viral infections and demyelinating diseases. New England Journal of Medicine 228:1103–1110
    [Google Scholar]
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