Spread of MHV-JHM from Nasal Cavity to White Matter of Spinal Cord

Transneuronal Movement and Involvement of Astrocytes
  • S. Perlman
  • N. Sun
  • E. M. Barnett
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 380)


C57B1/6 mice infected intranasally with mouse hepatitis virus, strain JHM (MHV-JHM) develop hindlimb paralysis with histological evidence of demyelination several weeks after inoculation. Virus must spread from the site of inoculation, the nasal cavity, to the site of disease, the white matter of the spinal cord. It has been shown previously that after intranasal inoculation, virus enters the brain via the olfactory nerve and spreads to infect many of its neuroanatomic connections within the central nervous system (CNS). In this report, it is shown that virus infecting the spinal cord is first detected in the gray matter, with spread occurring to the white matter soon thereafter. Astrocytes are heavily infected during the process of spread from the gray to the white matter of the spinal cord. Since astrocytes are in intimate contact with neuronal synapses and are themselves connected via gap junctions, these results suggest that astrocytes may be a conduit for the spread of virus in these mice. Astrocytes provide factors for the proliferation and survival of oligodendrocytes, and widespread infection of these cells might contribute to the demyelinating process eventually observed in these mice. Additionally, since virus first appears at specific locations in the spinal cord, it should be possible to determine the source of the virus infecting the cord. While the results are not definitive, the data are most consistent with virus spreading from the ventral reticular formation to the gray matter of the cervical spinal cord.


Spinal Cord White Matter Gray Matter Olfactory Bulb Nasal Cavity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Compton, S. R., Barthold, S. W., Smith, A. L. The celland molecular pathogenesis of coronaviruses. Lab. Anim. Sci. 1993;43:15–28.PubMedGoogle Scholar
  2. 2.
    Weiner, L. P. Pathogenesis of demyelination induced by a mouse hepatitisvirus (JHM virus). Arch. Neurol.1973;28:298–303.PubMedCrossRefGoogle Scholar
  3. 3.
    Parker, S. E., Gallagher, T. M., Buchmeier, M. J. Sequence analysisreveals extensive polymorphism and evidence of deletions within the E2glycoprotein gene of several strains of murine hepatitis virus. Virology 1989;173:664–673.PubMedCrossRefGoogle Scholar
  4. 4.
    Haspel, M. V., Lampert, P. W., Oldstone, M. B. A. Temperature-sensitivemutants of mouse hepatitis virus produce a highincidence of demyelination. Proc. Natl. Acad. Sci. 1978;75:4033–4036.PubMedCrossRefGoogle Scholar
  5. 5.
    Buchmeier, M. J., Lewicki, H. A., Talbot, P. J., Knobler, R. L. Murinehepatitis virus-4 (strain JHM)-induced neurologic disease is modulated in vivo bymonoclonal antibody. Virology 1984; 132:261–270.PubMedCrossRefGoogle Scholar
  6. 6.
    Stohlman, S. A., Matsushima, G. K., Casteel, N., Weiner,L. P. In vivo effects of coronavirus-specific T cell clones: DTH inducer cellsprevent a lethal infection but do not inhibit virus replication. J. Immunol. 1986;136:3052–3056.PubMedGoogle Scholar
  7. 7.
    Perlman, S., Schelper, R., Bolger, E., Ries, D. Lateonset, symptomatic, demyelinating encephalomyelitis in mice infected with MHV-JHM in the presence of maternal antibody.Microbial Pathog. 1987;2:185–194.CrossRefGoogle Scholar
  8. 8.
    Barnett, E. M., Perlman, S. The olfactory nerve and notthe trigeminal nerve is the major site of CNS entry for mouse hepatitis virus,strain JHM. Virology 1993;194:185–191.PubMedCrossRefGoogle Scholar
  9. 9.
    Sabin, A. B. Progression of different nasally instilledviruses along different nervous pathways in the same host. Proc. Soc. Exp. Med.Biol. 1938;38:270–275.Google Scholar
  10. 10.
    Barnett, E. M., Cassell, M., Perlman, S. Two neurotropic viruses,herpes simplex virus type I and mouse hepatitis virus,spread along different neural pathways from the main olfactory bulb. Neuroscience1993;157:1007–1025.CrossRefGoogle Scholar
  11. 11.
    Pasick, J., Kalicharran, K., Dales, S. Distribution andtrafficking of JHM coronavirus structural proteins and virions in primary neurons and the OBL-21 neuronal cell line. J.Virol. 1994;68:2915–2928.PubMedGoogle Scholar
  12. 12.
    Astic, 1., Saucier, D., Coulon, P., Lafay, F., Flamand, A. The CVSstrain of rabies virus as transneuronal tracer in the olfactory system of mice.Brain Res. 1993;619:146–156.PubMedCrossRefGoogle Scholar
  13. 13.
    Granum, S. L. The spinothalamic system of the rat. I. Locations of cellsof origin. J. Comp. Neurol. 1986;247:159–180.PubMedCrossRefGoogle Scholar
  14. 14.
    Burstein, R., Cliffer, K. D., Giesler, J., G.J. Cells of origin of thespinohypothalamic tract in the rat. J. Comp. Neurol. 1990;291:329–344.PubMedCrossRefGoogle Scholar
  15. 15.
    Cliffer, K. D., Burstein, R., Giesler, J., G. J. Distributions ofspinothalamic, spinohypothalamic and spinotelencephalicfibers revealed by anterorgrade transport of PHA-L in rats. J. Neurosci.1991;11:852–868.PubMedGoogle Scholar
  16. 16.
    Villanueva, L., de Pommery, J., Menetrey, D., Le Bars, D. Spinalafferent projections to subnucleus reticularis dorsalis in the rat.Neurosci. Lett. 1991;134:98–102.PubMedCrossRefGoogle Scholar
  17. 17.
    Yezierski, R. P., Mendez, C. M. Spinal distribution and collateralprojections of rat spinomesencephalic tract cells. Neuroscience1991;44:113–130.PubMedCrossRefGoogle Scholar
  18. 18.
    Mugaini, E. Cell junctions of astrocytes, ependyma and related cells inthe mammalian central nervous system, withe emphasis on the hypothesis of ageneralized functional syncytium of supporting cells. In: Fedoroff, S., Vernadakis, A.(eds) Astrocytes. Academic Press, New York1986 pp329-362.Google Scholar
  19. 19.
    Perlman, S., Ries, D. The astrocyte is a target cell inmice persistently infected with mouse hepatitis virus, strain JHM. MicrobialPathog. 1987;3:309–314.Google Scholar
  20. 20.
    Gallagher, T., Buchmeier, M., Perlman, S. Cellreceptor-independent infection by a neurotropic murine coronavirus.Virology 1992;191:517–522.PubMedCrossRefGoogle Scholar
  21. 21.
    Gard, A.L. Astrocyte-oligodendrocyte interactions. In: Murphy, S., (eds)Astrocytes: Pharmacology and Function. Academic Press, San Diego 1993 pp 331–354.Google Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • S. Perlman
    • 1
  • N. Sun
    • 1
  • E. M. Barnett
    • 1
  1. 1.Departments of Pediatrics and MicrobiologyUniversity of IowaIowa CityUSA

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