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. 1982 Nov;109(2):157–168.

Selected mutants of mouse hepatitis virus type 4 (JHM strain) induce different CNS diseases. Pathobiology of disease induced by wild type and mutants ts8 and ts15 in BALB/c and SJL/J mice.

R L Knobler, L A Tunison, P W Lampert, M B Oldstone
PMCID: PMC1916093  PMID: 6291396

Abstract

The model system of central nervous system (CNS) disease induced by mouse hepatitis virus type 4 (MHV-4) is explored by comparison of wild type (wt) MHV-4 and two temperature-sensitive (ts) mutants, designated ts8 and ts15, in BALB/c and SJL/J mice. In BALB/c mice, 3 plaque-forming units (PFU) of wt MHV-4 given intracerebrally caused fatal encephalomyelitis in all mice by 7 days after infection, with spread of virus outside the CNS, especially to liver. In SJL/J mice, 3 PFU of wt virus was cleared within 2-3 days, with little spread, and up tp 100 PFU failed to cause fatal encephalomyelitis. However, larger amounts of virus, like 1000 PFU, caused fatal encephalomyelitis in SJL/J mice. In contrast, 10(4) PFU of MHV-4 ts8 did not cause death in either BALB/c or SJL/J mice, and persisted in the CNS of both strains while retaining its ts phenotype. There was significatnly less spread of virus outside the CNS. BALB/c mice usually showed demyelination, remyelination, and recurrent demyelination with ts8, while SJL/J mice only rarely had lesions. Intracerebral inoculation with 10(4) PFU of MHV-4 ts15 was associated with a persistent infection in CNS and liver of BALB/c mice; however, only occasional demyelination and hepatic lesions occurred. TS15 did not cause death in either BALB/c or SJL/J mice and did not cause histopathologic injury in SJL/J mice.

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Selected References

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  1. Bailey D. W. Recombinant-inbred strains. An aid to finding identity, linkage, and function of histocompatibility and other genes. Transplantation. 1971 Mar;11(3):325–327. doi: 10.1097/00007890-197103000-00013. [DOI] [PubMed] [Google Scholar]
  2. Brown A. M., McFarlin D. E. Relapsing experimental allergic encephalomyelitis in the SJL/J mouse. Lab Invest. 1981 Sep;45(3):278–284. [PubMed] [Google Scholar]
  3. Collins A. R., Knobler R. L., Powell H., Buchmeier M. J. Monoclonal antibodies to murine hepatitis virus-4 (strain JHM) define the viral glycoprotein responsible for attachment and cell--cell fusion. Virology. 1982 Jun;119(2):358–371. doi: 10.1016/0042-6822(82)90095-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Haspel M. V., Lampert P. W., Oldstone M. B. Temperature-sensitive mutants of mouse hepatitis virus produce a high incidence of demyelination. Proc Natl Acad Sci U S A. 1978 Aug;75(8):4033–4036. doi: 10.1073/pnas.75.8.4033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Knobler R. L., Dubois-Dalcq M., Haspel M. V., Claysmith A. P., Lampert P. W., Oldstone M. B. Selective localization of wild type and mutant mouse hepatitis virus (JHM strain) antigens in CNS tissue by fluorescence, light and electron microscopy. J Neuroimmunol. 1981 Mar;1(1):81–92. doi: 10.1016/0165-5728(81)90010-2. [DOI] [PubMed] [Google Scholar]
  6. Knobler R. L., Haspel M. V., Oldstone M. B. Mouse hepatitis virus type 4 (JHM strains). induced fatal central nervous system disease. I. genetic control and murine neuron as the susceptible site of disease. J Exp Med. 1981 Apr 1;153(4):832–843. doi: 10.1084/jem.153.4.832. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Knobler R. L., Lampert P. W., Oldstone M. B. Virus persistence and recurring demyelination produced by a temperature-sensitive mutant of MHV-4. Nature. 1982 Jul 15;298(5871):279–280. doi: 10.1038/298279a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Lampert P. W., Sims J. K., Kniazeff A. J. Mechanism of demyelination in JHM virus encephalomyelitis. Electron microscopic studies. Acta Neuropathol. 1973 Mar 30;24(1):76–85. doi: 10.1007/BF00691421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. McCarthy K. D., de Vellis J. Preparation of separate astroglial and oligodendroglial cell cultures from rat cerebral tissue. J Cell Biol. 1980 Jun;85(3):890–902. doi: 10.1083/jcb.85.3.890. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Nagashima K., Wege H., Meyermann R., ter Meulen V. Demyelinating encephalomyelitis induced by a long-term corona virus infection in rats. A preliminary report. Acta Neuropathol. 1979 Mar 15;45(3):205–213. doi: 10.1007/BF00702672. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Powell H. C., Lampert P. W. Oligodendrocytes and their myelin-plasma membrane connections in JHM mouse hepatitis virus encephalomyelitis. Lab Invest. 1975 Oct;33(4):440–445. [PubMed] [Google Scholar]
  12. Sorensen O., Perry D., Dales S. In vivo and in vitro models of demyelinating diseases. III. JHM virus infection of rats. Arch Neurol. 1980 Aug;37(8):478–484. doi: 10.1001/archneur.1980.00500570026003. [DOI] [PubMed] [Google Scholar]
  13. Swank R. T., Bailey D. W. Recombinant inbred lines: value in the genetic analysis of biochemical variants. Science. 1973 Sep 28;181(4106):1249–1252. doi: 10.1126/science.181.4106.1249. [DOI] [PubMed] [Google Scholar]
  14. WAKSMAN B. H., ADAMS R. D. Infectious leukoencephalitis. A critical comparison of certain experimental and naturally-occurring viral leukoencephalitides with experimental allergic encephalomyelitis. J Neuropathol Exp Neurol. 1962 Oct;21:491–518. [PubMed] [Google Scholar]
  15. Weiner L. P. Pathogenesis of demyelination induced by a mouse hepatitis. Arch Neurol. 1973 May;28(5):298–303. doi: 10.1001/archneur.1973.00490230034003. [DOI] [PubMed] [Google Scholar]

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