1887

Abstract

The course of Semliki Forest virus (SFV) A7(74) infection in immunocompetent BALB/c, athymic and severe combined immunodeficient (SCID) mice was compared. BALB/c mice remained healthy and exhibited transient viraemia and infectious virus in the brain from days 2 to 7. Antibodies were detectable by day 5. In comparison, SCID mice displayed a high incidence of paralysis and died: the average day of death was day 23. From infection until death, virus was present in blood and brain. No antibodies were detectable. Athymic mice were intermediate with a transient viraemia and a persistent (> 210 days) sub-clinical central nervous system (CNS) infection. These mice produced anti-viral IgM but not IgG. The pattern of infection in BALB/c or mice could be recreated in infected SCID mice by transfer of immune serum from BALB/c or mice, with the important exception that although BALB/c immune serum could abolish infectivity titres in the CNS, scattered cells positive for viral RNA remained. Transfer of serum decreased mortality and delayed the onset of paralysis. Transfer to infected SCID mice of a non-neutralizing IgG anti-E2 monoclonal antibody did not affect the viraemia but could also reduce brain virus titres. Irrespective of specific immune responses, virus replication in CNS cells was restricted, was generally non-cytopathic and in the absence of specific immune responses could persist. From day 14 lesions of inflammatory, primary demyelination were observed throughout the CNS of BALB/c mice. In contrast, despite prolonged brain virus titres, no demyelinating lesions were observed in infected or SCID mice. Lesions could be initiated in the latter by transfer of spleen cells but not antibody. In summary, the focal restricted infection in the CNS of adult mice infected with SFV A7(74) is independent of specific immune responses. IgM antibodies clear the viraemia. IgG antibodies including non-neutralizing antibodies reduce and clear infectious virus but cells positive for viral RNA remain. These may normally be cleared by T cell responses which are damaging and give rise to lesions of demyelination.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-77-2-281
1996-02-01
2024-10-03
Loading full text...

Full text loading...

/deliver/fulltext/jgv/77/2/JV0770020281.html?itemId=/content/journal/jgv/10.1099/0022-1317-77-2-281&mimeType=html&fmt=ahah

References

  1. Amor S., Webb H. E. 1987; The effects of cycloleucine on SFV A7(74) infection in mice. British Journal of Experimental Pathology 68:225–235
    [Google Scholar]
  2. Bancroft G. J., Sheehan K. C. F., Schreiber R. D., Unanue E. R. 1987; A T cell-independent mechanism of macrophage activation by interferon-gamma. Journal of Immunology 139:1104–1107
    [Google Scholar]
  3. Bancroft G. J., Schreiber R. D., Bosma G. C., Bosma M. J., Unanue E. R. 1989; Tumor necrosis factor is involved in the T-cell independent pathway of macrophage activation by interferongamma. Journal of Immunology 143:127–130
    [Google Scholar]
  4. Barrett A. D. T., Cross A. J., Crow P. J., Johnson J. A., Guest A. R., Dimmock N. J. 1986; Subclinical infection in mice resulting from the modulation of a lethal dose of Semliki Forest virus with defective interfering viruses: neurochemical abnormalities in the central nervous system. Journal of General Virology 67:1727–1732
    [Google Scholar]
  5. Berger M. L. 1980; Humoral and cell mediated immune mechanisms in the production of pathology in avirulent Semliki Forest virus encephalitis. Infection and Immunity 30:244–253
    [Google Scholar]
  6. Buchmeier M. J., Lewicki H. A., Talbot P. J., Knobler R. L. 1984; Murine hepatitis virus-4 (strain JHM)-induced neurological disease is modulated in vivo by monoclonal antibody. Virology 132:261–270
    [Google Scholar]
  7. Chow L. H., Beisel K. W., McManus B. M. 1992; Enteroviral infection of mice with severe combined immunodeficiency. Evidence for direct viral pathogenesis of myocardial injury. Laboratory Investigation 66:24–31
    [Google Scholar]
  8. Fazakerley J. K., Webb H. E. 1987a; Semliki Forest virus induced, immune mediated demyelination: the effects of irradiation. British Journal of Experimental Pathology 68:101–113
    [Google Scholar]
  9. Fazakerley J. K., Webb H. E. 1987b; Semliki Forest virus induced, immune mediated demyelination: adoptive transfer studies and viral persistence in nude mice. Journal of General Virology 68:377–385
    [Google Scholar]
  10. Fazakerley J. K., Amor S., Webb H. E. 1983; Reconstitution of Semliki Forest virus infected mice, induces immune mediated pathological changes in the CNS. Clinical and Experimental Immunology 52:115–120
    [Google Scholar]
  11. Fazakerley J. K., Pathak S., Scallan M., Amor S., Dyson H. 1993; Replication of the A7(74) strain of Semliki Forest virus is restricted to neurons. Virology 195:627–637
    [Google Scholar]
  12. Fujinami R. S., Rosenthal A., Lampert P. W., Zurbriggen A., Yamada M. 1989; Survival of athymic (nu/nu) mice after Theiler’s murine encephalomyelitis virus infection by passive administration of neutralizing monoclonal antibody. Journal of Virology 63:2081–2087
    [Google Scholar]
  13. Jagelman S., Suckling A. J., Webb H. E., Bowen E. T. W. 1978; The pathogenesis of avirulent Semliki Forest virus infections in athymic nude mice. Journal of General Virology 41:599–607
    [Google Scholar]
  14. Kelly W. R., Blakemore W. F., Jagelman S., Webb H. E. 1982; Demyelination induced in mice by avirulent Semliki Forest virus. Part 2. An ultrastructural study of focal demyelination in the brain. Neuropathology and Applied Neurobiology 2:43–53
    [Google Scholar]
  15. Khalili-Shirazi A., Gregson N., Webb H. E. 1986; Immunological relationship between a demyelinating RNA enveloped budding virus (Semliki Forest) and brain glycolipids. Journal of Neurological Sciences 76:91–103
    [Google Scholar]
  16. Kim M. G., Schuler W., Bosma M. J., Marcus K. B. 1988; Aberrant Igh locus rearrangements in A-MuLV pre B lines of scid mice: evidence for deregulated D-J recombination. Current Topics in Microbiology and Immunology 137:203–210
    [Google Scholar]
  17. Kurtz C. I. B., Sun X. M., Fujinami R. S. 1995; Protection of SJL/J mice from demyelinating disease mediated by Theiler’s murine encephalomyelitis virus. Microbial Pathogenesis 18:11–27
    [Google Scholar]
  18. Levine B., Griffin D. E. 1992; Persistence of viral RNA in mouse brains after recovery from acute alphavirus infection. Journal of Virology 66:6429–6435
    [Google Scholar]
  19. Levine B., Hardwick J. M., Trapp B. D., Crawford T. O., Bollinger R. C., Griffin D. E. 1991; Antibody-mediated clearance of alphavirus infection from neurons. Science 254:856–860
    [Google Scholar]
  20. Levine B., Huang Q., Isaacs J. T., Reed J. C., Griffin D. E., Hardwick J. M. 1993; Conversion of lytic to persistent alphavirus infection by the bcl-2 cellular oncogene. Nature 361:739–742
    [Google Scholar]
  21. Liebert U. G., Schneider-Schaulies S., Baczko K., ter Meulen V. 1990; Antibody-induced restriction of viral gene expression in measles encephalitis in rats. Journal of Virology 64:706–713
    [Google Scholar]
  22. Lipkin W. I., Battenberg E. L. F., Bloom F. E., Oldstone M. B. A. 1988; Viral infection of neurons can depress neurotransmitter mRNA levels without histologic injury. Brain Research 451:333–339
    [Google Scholar]
  23. Malynn B. A., Blackwell T. K., Fulop G. M., Rathbun G. A., Furley A. J. W., Ferrier P., Heinke B., Phillips R. A., Yancopoulos G. D., Alt F. W. 1988; The scid defect affects the final step of the immunoglobulin VDJ recombinase mechanism. Cell 54:453–460
    [Google Scholar]
  24. Mehta S., Parsons L. M., Webb H. E. 1993; Effect of amitriptyline on neurotransmitter levels in mice following infection with the avirulent strain of Semliki Forest virus. Journal of Neurological Sciences 116:110–116
    [Google Scholar]
  25. Pathak S., Webb H. E., Oaten S. W., Bateman S. 1976; An electron-microscopic study of the development of virulent and avirulent strains of Semliki Forest virus in mouse brain. Journal of Neurological Sciences 28:289–300
    [Google Scholar]
  26. Pathak S., Webb H. E. 1978; An electron-microscopic study of avirulent and virulent Semliki Forest virus in the brains of different ages of mice. Journal of Neurological Sciences 39:199–211
    [Google Scholar]
  27. Pathak S., Webb H. E. 1980; The entry and the transport of arboviruses into and throughout mouse brain: an electron- microscopic study. Electron Microscopy 2:492–493
    [Google Scholar]
  28. Perry L. L., Lodmell D. L. 1991; Role of CD4+ and CD8+ T cells in murine resistance to street rabies virus. Journal of Virology 65:3429–3734
    [Google Scholar]
  29. Pusztai R., Gould E., Smith H. 1971; Infection pattern in mice of an avirulent and virulent strain of Semliki Forest virus. British Journal of Experimental Pathology 52:669–677
    [Google Scholar]
  30. Rozengurt N., Sanchez S. 1993; A spontaneous outbreak of Theiler’s encephalomyelitis in a colony of severe combined immunodeficient mice in the UK. Laboratory Animals 27:229–234
    [Google Scholar]
  31. Schuler W., Weiler I. J., Schuler A., Phillips R. A., Rosenberg N., Mak T. W., Kearney J. F., Perry R. P., Bosma M. J. 1986; Rearrangement of antigen receptor genes is defective in mice with severe combined immune deficiency. Cell 46:963–972
    [Google Scholar]
  32. Semenov B., Khozinsky V. V., Vargin V. V. 1975; The damaging action of cellular immunity in flavivirus infections of mice. Medical Biology 53:331–336
    [Google Scholar]
  33. Simas J. P., Dyson H., Fazakerley J. K. 1995; Molecular analysis of persistence, tropism and genetic variability of the BeAn strain of Theiler’s virus in the mouse CNS. Journal of Virology 69:5599–5606
    [Google Scholar]
  34. Subak-Sharpe L., Dyson H., Fazakerley J. K. 1993; In vivo depletion of CD8+ T cells prevents lesions of demyelination in Semliki Forest virus infection. Journal of Virology 67:7629–7633
    [Google Scholar]
  35. Suckling A. J., Pathak S., Jagelman S., Webb H. E. 1978; Virus associated demyelination: a model using avirulent Semliki Forest virus infection of mice. Journal of Neurological Sciences 36:147–154
    [Google Scholar]
  36. Tyler K. L., Virgin H. W., Bassel-Duby R., Fields B. N. 1989; Antibody inhibits defined stages in the pathogenesis of reovirus serotype 3 infection of the central nervous system. Journal of Experimental Medicine 170:887–900
    [Google Scholar]
  37. Wherry J. C., Schriber R. D., Unanue E. R. 1991; Regulation of gamma interferon production by natural killer cells in scid mice: role of tumor necrosis factor and bacterial stimuli. Infection and Immunity 59:1709–1715
    [Google Scholar]
/content/journal/jgv/10.1099/0022-1317-77-2-281
Loading
/content/journal/jgv/10.1099/0022-1317-77-2-281
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error