1887

Abstract

Murine gammaherpesvirus-68 (MHV-68) was originally isolated from a bank vole by passage through mouse brain. Given its ability to replicate in mouse brain and its subsequent reisolation from trigeminal ganglia, it was originally considered to be an alphaherpesvirus. Molecular studies have now firmly established MHV-68 to be a gammaherpesvirus. Other gammaherpesviruses have been suggested to cause and in some cases shown to cause neurological disease. Given the isolation history of MHV-68, we have studied the ability of this virus to gain access to, to replicate in and to persist in the mouse CNS. Following intranasal inoculation the virus was not generally neuroinvasive. However, in mice with a deletion of the type-I interferon receptor gene, peripheral virus titres are higher and perivascular CNS infection was observed. There was no evidence of virus spread via olfactory routes. Direct intracerebral inoculation of virus was fatal with widespread infection and destruction predominantly of meningeal and ependymal cells. Hippocampal pyramidal neurons, oligodendrocytes, Bergmann glia cells in the cerebellar cortex and neural progenitor cells in the rostral migratory stream were also infected. A similar infection was observed in younger mice. CNS infection following virus reactivation was investigated by implantation of infected glial cells. Implantation into a brain ventricle led to widespread fatal infection, principally involving ependymal and meningeal cells. Implantation into the striatum resulted in a predominantly neuronal infection. Implantation of cells into mice transiently treated with the antiviral thionucleoside analogue 2′-deoxy-5-ethyl-β-4′-thiouridine resulted in survival with detection of virus-infected cells in the brain 1 year later.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-81-11-2635
2000-11-01
2024-04-18
Loading full text...

Full text loading...

/deliver/fulltext/jgv/81/11/0812635a.html?itemId=/content/journal/jgv/10.1099/0022-1317-81-11-2635&mimeType=html&fmt=ahah

References

  1. Archard L. A., Bowles N. 1988; Detection of EBV-DNA in muscle biopsies of patients with postviral fatigue syndrome. Proceedings of the 3rd International Symposium on EBV and Associated Malignancies p 132
    [Google Scholar]
  2. Barnes A., Dyson H., Sunil-Chandra N. P., Collins P., Nash A. A. 1999; 2′-Deoxy-5-ethyl-beta-4′-thiouridine inhibits replication of murine gammaherpesvirus and delays the onset of virus latency. Antiviral Chemistry and Chemotherapy 10:321–326
    [Google Scholar]
  3. Blaskovic D., Stancekova M., Svobodova J., Mistrikova J. 1980; Isolation of five strains of herpesviruses from two species of free living small rodents. Acta Virologica 24:468
    [Google Scholar]
  4. Blaskovic D., Stanekova D., Rajcani J. 1984; Experimental pathogenesis of murine herpesvirus in newborn mice. Acta Virologica 28:225–231
    [Google Scholar]
  5. Borchers K., Wolfinger U., Ludwig H., Thein P., Baxi S., Field H. J., Slater J. D. 1998; Virological and molecular biological investigations into equine herpes virus type 2 (EHV-2) experimental infections. Virus Research 55:101–106
    [Google Scholar]
  6. Bowden R. J., Simas J. P., Davis A. J., Efstathiou S. 1997; Murine gammaherpesvirus-68 encodes tRNA-like sequences which are expressed during latency. Journal of General Virology 78:1675–1687
    [Google Scholar]
  7. Bray P. F., Culp K. W., McFarlin D. E., Panitch H. S., Torkelson R. D., Schlight A. 1992; Demyelinating disease after neurologically complicated EBV infection. Neurology 42:278–282
    [Google Scholar]
  8. Chan P. K. S., Ng H., Cheung J. L. K., Cheng A. F. 2000; Survey for the presence and distribution of human herpesvirus 8 in healthy brain. Journal of Clinical Microbiology 38:2772–2773
    [Google Scholar]
  9. Dutia B. M., Allen D. J., Dyson H., Nash A. A. 1999; Type I interferons and IRF-1 play a critical role in the control of a gammaherpesvirus infection. Virology 261:173–179
    [Google Scholar]
  10. Efstathiou S., Ho Y. M., Hall S., Styles C. J., Scott S. D., Gompels U. A. 1990; Murine herpesvirus 68 is genetically related to the gammaherpesviruses Epstein–Barr virus and herpesvirus saimiri. Journal of General Virology 71:1365–1372
    [Google Scholar]
  11. Egyed L., Bartha A. 1998; PCR studies on the potential sites for latency of BHV-4 in calves. Veterinary Research Communications 22:209–216
    [Google Scholar]
  12. Fazakerley J. K., Pathak S., Scallan M., Amor S., Dyson H. 1993; Replication of the A7(74) strain of Semliki Forest virus is restricted in neurons. Virology 195:627–637
    [Google Scholar]
  13. Flinn I. W., Ambinder R. F. 1996; AIDS primary central nervous system lymphoma. Current Opinion in Oncology 8:373–376
    [Google Scholar]
  14. Grant J. W., Isaacson P. G. 1992; Primary nervous system lymphoma. Brain Pathology 2:97–109
    [Google Scholar]
  15. Haahr S., Sommerlund M., Christensen T., Jensen A. W., Hansen H. J., Mollerlarsen A. 1994; A putative new retrovirus associated with multiple sclerosis and the possible involvement of Epstein–Barr virus in this disease. Annals of the New York Academy of Sciences 724:148–156
    [Google Scholar]
  16. Hickey W. F. 1999; Leukocyte traffic in the central nervous system: the participants and their roles. Seminars in Immunology 11:125–137
    [Google Scholar]
  17. Hotchin N. A., Read R., Smith D. G., Crawford D. H. 1989; Active Epstein–Barr virus infection in post-viral fatigue syndrome. Journal of Infectious Diseases 18:143–150
    [Google Scholar]
  18. Imai S., Usui N., Sugiura M., Osato T., Tsutsumi H., Tachi N., Nakata S., Yamanaka T., Chiba S., Shimada M. 1993; Epstein–Barr virus genomic sequences and specific antibodies in cerebrospinal fluid in children with neurologic complications of acute and reactivated EBV infections. Journal of Medical Virology 40:278–284
    [Google Scholar]
  19. Itoyama T., Sadamori N., Tsutsumi K., Tokunaga Y., Soda H., Tomonaga M., Yamamori S., Masuda Y., Oshima K., Kikuchi M. 1994; Primary CNS lymphomas. Immunophenotypic, virologic and cytogenetic findings of 3 patients without immune defects. Cancer 73:455–463
    [Google Scholar]
  20. Knopf P. P., Harling-Berg C. J., Cserr H. F., Sirulnick R. J., Nolan S. C., Park J. T., Keir G., Thompson E. J., Hickey W. F. 1998; Antigen dependent intrathecal antibody synthesis in the normal rat brain: tissue entry and local retention of antigen-specific B cell. Journal of Immunology 161:692–701
    [Google Scholar]
  21. Martyn C. N., Cruddas M., Compston D. A. S. 1993; Symptomatic Epstein–Barr virus infection and multiple sclerosis. Journal of Neurology, Neurosurgery and Psychiatry 56:167–168
    [Google Scholar]
  22. Muller U., Steinhoff U., Reis L., Hemmi S., Pavlovic J., Zinkernagel R. M., Auget M. 1994; Functional role of type I and type II interferons in antiviral defense. Science 264:1918–1921
    [Google Scholar]
  23. Nash A. A., Usherwood E. J., Stewart J. P. 1996; Immunological features of murine gammaherpesvirus infection. Seminars in Virology 7:125–130
    [Google Scholar]
  24. Raible D. W., McMorris F. A. 1989; Cyclic AMP regulates the rate of differentiation of oligodendrocytes without changing the lineage commitment of their progenitors. Developmental Biology 133:437–446
    [Google Scholar]
  25. Rajcani J., Blaskovic D., Svobodova J., Ciampor F., Huckova D., Stanekova D. 1985; Pathogenesis of acute and persistent murine herpesvirus infection in mice. Acta Virologica 29:51–60
    [Google Scholar]
  26. Rizvi S. M., Slater J. D., Slade A. J., Field H. J. 1997a; Transmission of equine herpesvirus 2 to the mouse: characterization of a new laboratory infection model. Journal of General Virology 78:1119–1124
    [Google Scholar]
  27. Rizvi S. M., Slater J. D., Wolfinger U., Borchers K., Field H. J., Slade A. J. 1997b; Detection and distribution of equine herpesvirus 2 DNA in the central nervous system of ponies. Journal of General Virology 78:1115–1118
    [Google Scholar]
  28. Roberg M., Ernerudh J., Forsberg P., Fridell E., Fryden E., Hyden D., Linde A., Odkvist L. 1991; Acute facial palsy: CSF findings and aetiology. Acta Neurologica Scandinavica 83:55–60
    [Google Scholar]
  29. Ryman K. D., Klimstra W. B., Nguyen K. B., Biron C. A., Johnston R. E. 2000; Alpha/beta interferon protects adult mice from fatal Sindbis virus infection and is an important determinant of cell and tissue tropism. Journal of Virology 74:3366–3378
    [Google Scholar]
  30. Stewart J. P. 1999; Of mice and men: murine gammaherpesvirus 68 as a model. Epstein–Barr Virus Report 6:31–35
    [Google Scholar]
  31. Stewart J. P., Usherwood E. J., Ross A., Dyson H., Nash T. 1998; Lung epithelial cells are a major site of murine gammaherpesvirus persistence. Journal of Experimental Medicine 187:1941–1951
    [Google Scholar]
  32. Sunil-Chandra N. P., Efstathiou S., Arno J., Nash A. A. 1992a; Virological and pathological features of mice infected with murine gammaherpesvirus 68. Journal of General Virology 73:2347–2356
    [Google Scholar]
  33. Sunil-Chandra N. P., Efstathiou S., Nash A. A. 1992b; Murine gammaherpesvirus 68 establishes a latent infection in mouse B lymphocytes in vivo. Journal of General Virology 73:3275–3279
    [Google Scholar]
  34. Sunil-Chandra N. P., Arno J., Fazakerley J. K., Nash A. A. 1994; Lymphoproliferative disease in mice infected with murine gammaherpesvirus 68. American Journal of Pathology 145:818–826
    [Google Scholar]
  35. Svobodova J., Blaskovic D., Mistrikova J. 1982; Growth characteristics of herpesviruses isolated from free living small rodents. Acta Virologica 26:256–263
    [Google Scholar]
  36. Terry L. A., Usherwood E. J., Lees S. J., MacIntyre N., Nash A. A. 1997; Immune response to murine cell lines of glial origin transplanted into the central nervous system of adult mice. Immunology 91:436–443
    [Google Scholar]
  37. Usherwood E. J., Stewart J. P., Nash A. A. 1996; Characterization of tumor cell lines derived from murine gammaherpesvirus-68-infected mice. Journal of Virology 70:6516–6518
    [Google Scholar]
  38. Virgin H. W., Latreille P., Wamsley P., Hallsworth K., Weck K. E., Dal Canto A. J., Speck S. H. 1997; Complete sequence and genomic analysis of murine gammaherpesvirus 68. Journal of Virology 71:5894–5904
    [Google Scholar]
  39. Weck K. E., Kim S. S., Virgin H. W. I., Speck S. H. 1999; Macrophages are the major reservoir of latent murine gammaherpesvirus 68 in peritoneal cells. Journal of Virology 73:3273–3283
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-81-11-2635
Loading
/content/journal/jgv/10.1099/0022-1317-81-11-2635
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