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. 2004 Apr 15;2(3):185–194. doi: 10.1016/0882-4010(87)90020-9

Late onset, symptomatic, demyelinating encephalomyelitis in mice infected with MHV-JHM in the presence of maternal antibody

S Perlman 1,, R Schelper 2, E Bolger 2, D Ries 1
PMCID: PMC7135528  PMID: 2853274

Abstract

The presence of maternal antibodies protected suckling C57BL/6 mice from the clinical manifestations of the acute encephalomyelitis caused by mouse hepatitis virus, strain JHM (MHV-JHM), a coronavirus, even though histological evidence of encephalomyelitis was found at early times after inoculation. 100% of infected suckling mice developed a fatal disease in the absence of maternal antibody. By 14 days after inoculation, the brains of all antibody-protected mice examined were nearly normal on histological examination. At 3–8 weeks post-inoculation, approximately 40% of the antibody-protected mice developed a neurological disease characterized by hindlimb paralysis and wasting. Evidence of inflammation and demyelination was apparent in the spinal cord and brainstem. The mice that remained asymptomatic at this time showed few signs of inflammation and none developed clinical disease over the following 9 months. Viral antigen could be detected in most of the mice examined at all times after inoculation, whether symptomatic or not, and was particularly evident in the animals with hindlimb paralysis. MHV-JHM could be consistently cultured from the mice with hindlimb paralysis. These results show that maternal immune factors can completely protect susceptible mice from the acute, fatal, clinical encephalomyelitis caused by MHV-JHM, but cannot prevent the establishment of a latent state and subsequent development of virus-induced, clinically evident, demyelinating disease. This model will be useful for studying the virus and host factors important for the development of MHV-JHM latency and subsequent virus-induced demyelination.

Keywords: mouse hepatitis virus, demyelination, maternal antibody, immunoperoxidase

Footnotes

The investigation was supported in part by N.I.H. Biomedical Research Grant RR 05372.

References

  • 1.Lampert PW. Autoimmune and virus-induced demyelinating diseases. A review. Am J Path. 1978;91:176–197. [PMC free article] [PubMed] [Google Scholar]
  • 2.Siddell S, Wege H, ter Meulen V. The biology of coronaviruses. J Gen Virol. 1983;64:761–776. doi: 10.1099/0022-1317-64-4-761. [DOI] [PubMed] [Google Scholar]
  • 3.Cheever FS, Daniels JB, Pappenheimer AM, Bailey OT. A murine virus (JHM) causing disseminated encephalomyelitis with extensive destruction of myelin. J Exp Med. 1949;90:181–194. doi: 10.1084/jem.90.3.181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Herndon RM, Griffin DE, McCormick V, Weiner LP. Mouse hepatitis virus-induced recurrent demyelination. Arch Neurol. 1975;32:32–35. doi: 10.1001/archneur.1975.00490430054008. [DOI] [PubMed] [Google Scholar]
  • 5.Lampert PW, Sims JK, Kniazeff AJ. Mechanism of demyelination in JHM virus encephalomyelitis. Acta Neuropath. 1973;24:76–85. doi: 10.1007/BF00691421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Nagashima K, Wege H, Meyeremann R, ter Meulen V. Coronavirus induced subacute demyelinating encephalomyelitis in rats. A morphological analysis. Acta Neuropathol (Berl) 1978;44:63–70. doi: 10.1007/BF00691641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Nagashima K, Wege R, Meyermann R, ter Meulen V. Demyelinating encephalomyelitis induced by long term coronavirus infection in rats. Acta Neuropathol (Berl) 1979;45:205–213. doi: 10.1007/BF00702672. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Sorensen O, Perry D, Dales S. In vivo and in vitro models of demyelinating diseases. III. JHM virus infection of rats. Arch Neurol. 1980;37:478–484. doi: 10.1001/archneur.1980.00500570026003. [DOI] [PubMed] [Google Scholar]
  • 9.Stohlman SA, Weiner LP. Chronic central nervous system demyelination in mice after JHM virus infection. Neurology. 1981;31:38–44. doi: 10.1212/wnl.31.1.38. [DOI] [PubMed] [Google Scholar]
  • 10.Weiner LP. Pathogenesis of demyelination induced by a mouse hepatitis virus. Arch Neurol. 1973;28:298–303. doi: 10.1001/archneur.1973.00490230034003. [DOI] [PubMed] [Google Scholar]
  • 11.Buchmeier MJ, Lewicki HA, Talbot PJ, Knobler RL. Murine hepatitis virus-4 (strain JHM)-induced neurological disease is modulated in vivo by monoclonal antibody. Virology. 1984;132:261–270. doi: 10.1016/0042-6822(84)90033-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Pickel K, Muller MA, ter Meulen V. Influence of maternal immunity on the outcome of murine coronavirus JHM infection in suckling mice. Med Microbiol Immunol. 1985;174:15–24. doi: 10.1007/BF02123666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Halliday R. The effect of steroid hormones on the absorption of antibody by the young rat. J Endocrin. 1959;18:56–66. doi: 10.1677/joe.0.0180056. [DOI] [PubMed] [Google Scholar]
  • 14.Hall WW, Choppin PW. Measles-virus proteins in the brain tissue of patients with subacute sclerosing panencephalitis. Absence of the M protein. N Engl J Med. 1971;304:1152–1155. doi: 10.1056/NEJM198105073041906. [DOI] [PubMed] [Google Scholar]
  • 15.Johnson KP, Norrby E, Swoveland P, Carrigan DR. Experimental subacute sclerosing panencephalitis: Selective disappearance of measles virus matrix protein from the central nerous system. J Infect Dis. 1981;144:161–169. doi: 10.1093/infdis/144.2.161. [DOI] [PubMed] [Google Scholar]
  • 16.Rammohan KW, McFarland HF, McFarlin DE. Subacute sclerosing panencephalitis after passive immunization and natural measles infection: role of antibody in persistence of measles virus. Neurology. 1982;32:390–394. doi: 10.1212/wnl.32.4.390. [DOI] [PubMed] [Google Scholar]
  • 17.Stohlman SA, Sakaguchi AY, Weiner LP. Characterization of the cold-sensitive murine hepatitis virus mutants rescued from latently infected cells by cell fusion. Virology. 1979;98:448–455. doi: 10.1016/0042-6822(79)90567-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Pace MG, Dresser DW. The elimination of mouse and bovine globulins from the circulation of newborn and adult mice. Quart J Exp Physiol. 1961;46:369–375. [Google Scholar]
  • 19.Jackson DP, Percy DH, Morris VL. Characterization of murine hepatitis virus (JHM) RNA from rats with experimental encephalomyelitis. Virology. 1984;137:297–304. doi: 10.1016/0042-6822(84)90221-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Taguchi F, Siddell SG, Wege H, ter Meulen V. Characterization of a variant virus selected in rat brains after infection by coronavirus mouse hepatitis virus JHM. J Virol. 1985;54:429–435. doi: 10.1128/jvi.54.2.429-435.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Lavi E, Gilden D, Wroblewska Z, Rorke L, Weiss SR. Experimental demyelination produced by the A59 strain of mouse hepatitis virus. Neurology. 1984;34:597–603. doi: 10.1212/wnl.34.5.597. [DOI] [PubMed] [Google Scholar]
  • 22.Lavi E, Gilden DH, Highkin MK, Weiss SR. Persistence of mouse hepatitis virus A59 RNA in a slow virus demyelinating infection in mice as detected by in situ hybridization. J Virol. 1984;51:563–566. doi: 10.1128/jvi.51.2.563-566.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Lennette EH, Schmidt NJ. American Public Health Association; New York: 1969. Diagnostic procedures for viral and rickettsial infections; p. 446. [Google Scholar]

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