Summary
Mouse hepatitis virus 3 (MHV 3) is either avirulent (resistant mice), hepatotropic (susceptible mice). or neurotropic (semisusceptible mice), depending on the strain of mice infected. In semisusceptible mice, infection led first to a transient meningitis, ependymitis, and leukoencephalitis, followed by a permanent communicating hydrocephalus and, later on, to a chronic thrombotic vasculitis affecting meningeal and parenchymal vessels at the brain stem level. Small foci of ischemic necrosis related to vascular occlusions were seen in the dorsal brain stem. Cyclophosphamide treatment of semisusceptible mice significantly reduced the meningeal infiltrates but did not prevent the development of hydrocephalus and other neuropathologic changes. Identical lesions occurred in fully susceptible mice infected with a low dose of virus, but no neurologic disorder could be induced in genetically resistant mice even following immunosuppression or intracranial inoculation. The leukoencephalitis differed from the demyelinating lesions observed with MHV4. Vascular lesions were of particular interest. More attention should be given to the possibifity of virus induced chronic cerebral vasculitis in man.
Key words: MHV 3, Viral vasculitis, Experimental hydrocephalus, Experimental leukoencephalitis
Footnotes
Supported by the Fonds National de la Recherche Scientifique, Belgium, grant no. 3.4540.81, by the Fonds de Développement Scientifique, Faculté de Médecine, Université de Louvain, and by INSERM contract CRL 826036
References
- Allison AC. Genetic factors in resistance against virus infection. Arch Gesamte Virusforsch. 1965;17:280–293. doi: 10.1007/BF01267912. [DOI] [PubMed] [Google Scholar]
- Dupuy JM, Le Prevost C, Levy-Leblond E, Virelizier J. Persistent virus infection with neurological involvement in mice infected with MHV 3. Fed Proc. 1973;32:4179–4187. [Google Scholar]
- Dupuy JM, Levy-Leblond E, Le Prevost C. Immunopathology of mouse hepatitis virus type 3 infection. II. Effect of immunosuppression in resistant mice. J Immunol. 1975;114:226–230. [PubMed] [Google Scholar]
- Esiri MM. Poliomyelitis: immunoglobulin-containing cells in the central nervous system in acute and convalescent phases of the human disease. Clin Exp Immunol. 1980;40:42–48. [PMC free article] [PubMed] [Google Scholar]
- Haspel MV, Lampert PW, Oldstone MBA. Temperaturesensitive mutants of mouse hepatitis virus produce a high incidence of demyelination. Proc Natl Acad Sci. 1978;15:4033–4036. doi: 10.1073/pnas.75.8.4033. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Herndon RM, Griffin DE, Melormick U, Weiner LP. MHV-induced recurrent demyelination. A preliminary report. Arch Neurol. 1975;32:32–35. doi: 10.1001/archneur.1975.00490430054008. [DOI] [PubMed] [Google Scholar]
- Hirsch MS, Zisman B, Allison AC. Macrophages and agedependent resistance to herpes simplex virus in mice. J Immunol. 1970;104:1160–1165. [PubMed] [Google Scholar]
- Johnson RT. The pathogenesis of herpes virus encephalitis. I. Virus pathways to the nervous system of suckling mice demonstrated by fluorescent antibody staining. J Exp Med. 1964;119:343–358. doi: 10.1084/jem.119.2.343. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Johnson RT, Johnson KP, Edmonds CJ. Virus induced hydrocephalus: development of aqueductal stenosis in hamster after mumps infection. Science. 1967;157:1066–1067. doi: 10.1126/science.157.3792.1066. [DOI] [PubMed] [Google Scholar]
- Johnson RT, Johnson KP. Hydrocephalus following viral infections: the pathology of aqueductal stenosis developing after experimental mumps virus infection. J Neuropathol Exp Neurol. 1968;27:591–603. [PubMed] [Google Scholar]
- Johnson RT. Hydrocephalus and viral infections. Develop Med Child Neurol. 1975;17:807–816. doi: 10.1111/j.1469-8749.1975.tb04710.x. [DOI] [PubMed] [Google Scholar]
- Kolodny EH, Rebeiz JJ, Caviness VS, Richardson EP. Granulomatous angiitis of the central nervous system. Arch Neurol. 1968;19:510–524. doi: 10.1001/archneur.1968.00480050080008. [DOI] [PubMed] [Google Scholar]
- Kumar V, Bennett M, Eckner RJ. Mechanism of genetic resistance to Friend leukemia virus in mice. I. Role of89Srsensitive effector cells responsible for rejection of bone marrow allografts. J Exp Med. 1976;139:1093–1109. [Google Scholar]
- Lampert PW, Sims JK, Kniazeff AJ. Mechanism of demyelination in JHM virus encephalomyelitis. Electronmicroscopic studies. Acta Neuropathol (Berl) 1973;24:76–85. doi: 10.1007/BF00691421. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Le Prevost C, Levy-Leblond E, Virelizier JL, Dupuy JM. Immunopathology of mouse hepatitis virus type 3 infection. I. Role of humoral and cell-mediated immunity in resistance mechanisms. J Immunol. 1975;114:221–225. [PubMed] [Google Scholar]
- Le Prevost C, Virelizier JL, Dupuy JM. Immunopathology of mouse hepatitis virus type 3 infection. III. Clinical and virologic observations of a peristent viral infection. J Immunol. 1975;115:640–643. [PubMed] [Google Scholar]
- Levy-Leblond E, Oth D, Dupuy JM. Genetic study of mouse sensitivity to HMV 3 infection: influence of the H-2 complex. J Immunol. 1979;122:1359–1362. [PubMed] [Google Scholar]
- Linnemann CC, Alvira MM. Pathogenesis of varicella-zoster angiitis in the CNS. Arch Neurol. 1980;37:239–240. doi: 10.1001/archneur.1980.00500530077013. [DOI] [PubMed] [Google Scholar]
- Masters C, Alpers M, Kakulas B. Pathogenesis of reovirus type I hydrocephalus in mice. Significance of aqueductal change. Arch Neurol. 1977;34:18–28. doi: 10.1001/archneur.1977.00500130038008. [DOI] [PubMed] [Google Scholar]
- Nielsen SL, Baringer JR. Reovirus-induced aqueductal stenosis in hamsters. Phase contrast and electron-microscopic studies. Lab Invest. 1972;27:531–537. [PubMed] [Google Scholar]
- Reyes MG, Fresco R, Chokroverty S, Salud EQ. Virus-like particles in granulomatous angiitis of the central nervous system. Neurology. 1976;26:797–799. doi: 10.1212/wnl.26.8.797. [DOI] [PubMed] [Google Scholar]
- Rorke LB, Spiro AJ. Cerebral lesions in congenital rubella syndrome. J Pediatr. 1967;70:243–255. doi: 10.1016/s0022-3476(67)80419-0. [DOI] [PubMed] [Google Scholar]
- Rorke LB, Fabiyi A, Elizan TS, Sever JL. Experimental cerebrovascular lesions in congenital and neonatal rubella-virus infections of ferrets. Lancet. 1968;1:153–154. doi: 10.1016/s0140-6736(68)90428-5. [DOI] [PubMed] [Google Scholar]
- Rorke LB. Nervous system lesions in the congenital rubella syndrome. Arch Otolaryngol. 1973;98:249–251. doi: 10.1001/archotol.1973.00780020259007. [DOI] [PubMed] [Google Scholar]
- Rosenblum WI, Hodfield MG. Granulomatous angiitis of the nervous system in cases of herpes zoster and lymphosarcoma. Neurology. 1972;22:348–354. doi: 10.1212/wnl.22.4.348. [DOI] [PubMed] [Google Scholar]
- Singer DB, Rudolph PJ, Rosenberg HS, Rawls WF, Boniuk M. Pathology of the congenital rubella syndrome. J Pediat. 1967;71:665–675. doi: 10.1016/s0022-3476(67)80202-6. [DOI] [PubMed] [Google Scholar]
- Stockman GD, Heim LR, South MA, Trentin JJ. Differential effects of cyclophosphamide on the B- and T-cell compartments of adult mice. J Immunol. 1973;110:277–282. [PubMed] [Google Scholar]
- Stohlman SA, Weiner LP. Chronic central nervous system demyclination in mice after JHM virus infection. Neurology. 1981;31:38–44. doi: 10.1212/wnl.31.1.38. [DOI] [PubMed] [Google Scholar]
- Tardieu M, Hery C, Dupuy JM. Neonatal susceptibility to MHV 3 infection in mice. II. Role of natural effector marrow cells in transfer of resistance. J Immunol. 1980;124:418–423. [PubMed] [Google Scholar]
- Virelizier JL, Dayan AD, Allison AC. Neuropathological effects of persistent infection of mice by mouse hepatitis virus. Infect Immun. 1975;12:1127–1140. doi: 10.1128/iai.12.5.1127-1140.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Waksman BH, Adams RD. Infectious leukoencephalitis. A critical comparison of certain experimental and naturallyoccuring viral leukoencephalitis with experimental allergic encephalomyelitis. J Neuropathol Exp Neurol. 1962;21:491–518. [PubMed] [Google Scholar]
- Weiner LP. Pathogenesis of demyelination induced by a mouse hepatitis virus (JHM virus) Arch Neurol. 1973;28:298–303. doi: 10.1001/archneur.1973.00490230034003. [DOI] [PubMed] [Google Scholar]
- Weiner HL, Drayna D, Averill DR, Fields BN. Molecular basis of reovirus virulence: role of the S1 gene. Proc Natl Acad Sci (USA) 1977;74:5744–5748. doi: 10.1073/pnas.74.12.5744. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weiner LP, Stohlman SA. Viral models of demyelination. Neurology. 1978;28:111–114. doi: 10.1212/wnl.28.9_part_2.111. [DOI] [PubMed] [Google Scholar]
- Willenborg DO, Shah KV, Bang FB. Effect of cyclophosphamide on the genetic resistance of C3H mice to mouse hepatitis virus. Proc Soc Exp Biol Med. 1973;142:762–766. doi: 10.3181/00379727-142-37111. [DOI] [PubMed] [Google Scholar]
- Wolinsky JS. Mumps virus-induced hydrocephalus in hamsters. Ultrastructure of the chronic infection. Lab Invest. 1977;37:229–236. [PubMed] [Google Scholar]
- Wolinsky JS, Stroop WG. Virulence and persistence of three prototype strains of mumps virus in newborn hamster. Arch Virol. 1978;57:355–359. doi: 10.1007/BF01320075. [DOI] [PubMed] [Google Scholar]
