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. 1991 Jan;65(1):123–131. doi: 10.1128/jvi.65.1.123-131.1991

Penetration of the nervous systems of suckling mice by mammalian reoviruses.

A Flamand 1, J P Gagner 1, L A Morrison 1, B N Fields 1
PMCID: PMC240496  PMID: 1845880

Abstract

Penetration of the nervous systems of suckling mice by prototype strains of the three mammalian reovirus serotypes was studied after footpad inoculation of a dose (10(7) PFU) representing 3.5 x 10(3) 50% lethal doses (LD50) for reovirus type 3 Dearing and less than 1 LD50 for reoviruses type 1 Lang and type 2 Jones. Type 3 Dearing entered both motor and sensory neurons; infected neurons were clearly detectable by immunohistochemical staining 19 h after inoculation. By day 2, a second cycle of infection had occurred, and by day 4, several hundred motor and sensory neurons and interneurons were infected. By this time, infection also involved large areas of the brain stem and brain. There was evidence of both retrograde and anterograde movement of viral antigen within axons and dendrites. Unexpectedly, reovirus type 1 Lang followed neuronal pathways as well as being disseminated in the bloodstream. Reovirus type 2 Jones also entered neurons. While the number of motor neurons and interneurons infected with type 1 Lang or type 2 Jones remained limited within the first 4 days after inoculation, infection of sensory neurons increased with time and reached a level by day 4 comparable to that observed after infection with type 3 Dearing. Viral antigen was also found in the brain stem and brain, but this infection was limited. These three strains multiplied in nonneuronal tissues. Connective tissue in the footpad was massively infected by all three strains 19 h after inoculation. By this time, foci of infection were also present in muscle and skin. Viral antigen was repeatedly observed in the endothelium of blood vessels and in the meninges after infection with type 1 Lang. The titer of type 1 Lang increased in the blood with time, which was not observed after infection with strains of the other two serotypes. In this study, we found that prototype strains of the three reovirus serotypes exhibited different degrees of neurotropism, all being capable of entering neurons. Transmission of the infection occurred through synapses rather than from cell body to cell body. Thus reovirus, like herpesvirus and rabies virus, is a good marker for the identification of neuronal pathways, although its capacity to grow in neurons, unlike that of herpesvirus and rabies virus, is restricted to newborn animals.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bass D. M., Trier J. S., Dambrauskas R., Wolf J. L. Reovirus type I infection of small intestinal epithelium in suckling mice and its effect on M cells. Lab Invest. 1988 Feb;58(2):226–235. [PubMed] [Google Scholar]
  2. Bodkin D. K., Nibert M. L., Fields B. N. Proteolytic digestion of reovirus in the intestinal lumens of neonatal mice. J Virol. 1989 Nov;63(11):4676–4681. doi: 10.1128/jvi.63.11.4676-4681.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Coulon P., Derbin C., Kucera P., Lafay F., Prehaud C., Flamand A. Invasion of the peripheral nervous systems of adult mice by the CVS strain of rabies virus and its avirulent derivative AvO1. J Virol. 1989 Aug;63(8):3550–3554. doi: 10.1128/jvi.63.8.3550-3554.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Furlong D. B., Nibert M. L., Fields B. N. Sigma 1 protein of mammalian reoviruses extends from the surfaces of viral particles. J Virol. 1988 Jan;62(1):246–256. doi: 10.1128/jvi.62.1.246-256.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hrdy D. B., Rubin D. H., Fields B. N. Molecular basis of reovirus neurovirulence: role of the M2 gene in avirulence. Proc Natl Acad Sci U S A. 1982 Feb;79(4):1298–1302. doi: 10.1073/pnas.79.4.1298. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Jenson A. B., Rabin E. R., Bentinck D. C., Rapp F. Reovirus viremia in newborn mice. An electron microscopic, immunofluorescent and virus assay study. Am J Pathol. 1966 Dec;49(6):1171–1183. [PMC free article] [PubMed] [Google Scholar]
  7. Kilham L., Margolis G. Hydrocephalus in hamsters, ferrets, rats, and mice following inoculations with reovirus type I. I. Virologic studies. Lab Invest. 1969 Sep;21(3):183–188. [PubMed] [Google Scholar]
  8. Kristensson K., Nennesmo L., Persson L., Lycke E. Neuron to neuron transmission of herpes simplex virus. Transport of virus from skin to brainstem nuclei. J Neurol Sci. 1982 Apr;54(1):149–156. doi: 10.1016/0022-510x(82)90227-1. [DOI] [PubMed] [Google Scholar]
  9. Kundin W. D., Liu C., Gigstad J. Reovirus infection in suckling mice: immunofluorescent and infectivity studies. J Immunol. 1966 Sep;97(3):393–401. [PubMed] [Google Scholar]
  10. Kuypers H. G., Ugolini G. Viruses as transneuronal tracers. Trends Neurosci. 1990 Feb;13(2):71–75. doi: 10.1016/0166-2236(90)90071-h. [DOI] [PubMed] [Google Scholar]
  11. Lee P. W., Hayes E. C., Joklik W. K. Protein sigma 1 is the reovirus cell attachment protein. Virology. 1981 Jan 15;108(1):156–163. doi: 10.1016/0042-6822(81)90535-3. [DOI] [PubMed] [Google Scholar]
  12. Margolis G., Kilham L. Hydrocephalus in hamsters, ferrets, rats, and mice following inoculations with reovirus type I. II. Pathologic studies. Lab Invest. 1969 Sep;21(3):189–198. [PubMed] [Google Scholar]
  13. Ramig R. F., Mustoe T. A., Sharpe A. H., Fields B. N. A genetic map of reovirus. II. Assignment of the double-stranded RNA-negative mutant groups C, D, and E to genome segments. Virology. 1978 Apr;85(2):531–534. doi: 10.1016/0042-6822(78)90459-2. [DOI] [PubMed] [Google Scholar]
  14. Tardieu M., Powers M. L., Weiner H. L. Age dependent susceptibility to Reovirus type 3 encephalitis: role of viral and host factors. Ann Neurol. 1983 Jun;13(6):602–607. doi: 10.1002/ana.410130604. [DOI] [PubMed] [Google Scholar]
  15. Tyler K. L., Bronson R. T., Byers K. B., Fields B. Molecular basis of viral neurotropism: experimental reovirus infection. Neurology. 1985 Jan;35(1):88–92. doi: 10.1212/wnl.35.1.88. [DOI] [PubMed] [Google Scholar]
  16. Tyler K. L., McPhee D. A., Fields B. N. Distinct pathways of viral spread in the host determined by reovirus S1 gene segment. Science. 1986 Aug 15;233(4765):770–774. doi: 10.1126/science.3016895. [DOI] [PubMed] [Google Scholar]
  17. Tyler K. L., Virgin H. W., 4th, Bassel-Duby R., Fields B. N. Antibody inhibits defined stages in the pathogenesis of reovirus serotype 3 infection of the central nervous system. J Exp Med. 1989 Sep 1;170(3):887–900. doi: 10.1084/jem.170.3.887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ugolini G., Kuypers H. G., Simmons A. Retrograde transneuronal transfer of herpes simplex virus type 1 (HSV 1) from motoneurones. Brain Res. 1987 Oct 6;422(2):242–256. doi: 10.1016/0006-8993(87)90931-0. [DOI] [PubMed] [Google Scholar]
  19. Ugolini G., Kuypers H. G., Strick P. L. Transneuronal transfer of herpes virus from peripheral nerves to cortex and brainstem. Science. 1989 Jan 6;243(4887):89–91. doi: 10.1126/science.2536188. [DOI] [PubMed] [Google Scholar]
  20. Verdin E. M., Lynn S. P., Fields B. N., Maratos-Flier E. Uptake of reovirus serotype 1 by the lungs from the bloodstream is mediated by the viral hemagglutinin. J Virol. 1988 Feb;62(2):545–551. doi: 10.1128/jvi.62.2.545-551.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Virgin H. W., 4th, Bassel-Duby R., Fields B. N., Tyler K. L. Antibody protects against lethal infection with the neurally spreading reovirus type 3 (Dearing). J Virol. 1988 Dec;62(12):4594–4604. doi: 10.1128/jvi.62.12.4594-4604.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. WALTERS M. N., LEAK P. J., JOSKE R. A., STANLEY N. F., PERRET D. H. MURINE INFECTION WITH REOVIRUS. 3. PATHOLOGY OF INFECTION WITH TYPES 1 AND 2. Br J Exp Pathol. 1965 Apr;46:200–212. [PMC free article] [PubMed] [Google Scholar]
  23. Weiner H. L., Ault K. A., Fields B. N. Interaction of reovirus with cell surface receptors. I. Murine and human lymphocytes have a receptor for the hemagglutinin of reovirus type 3. J Immunol. 1980 May;124(5):2143–2148. [PubMed] [Google Scholar]
  24. Weiner H. L., Drayna D., Averill D. R., Jr, Fields B. N. Molecular basis of reovirus virulence: role of the S1 gene. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5744–5748. doi: 10.1073/pnas.74.12.5744. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Weiner H. L., Powers M. L., Fields B. N. Absolute linkage of virulence and central nervous system cell tropism of reoviruses to viral hemagglutinin. J Infect Dis. 1980 May;141(5):609–616. doi: 10.1093/infdis/141.5.609. [DOI] [PubMed] [Google Scholar]

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