Skip to main content
PMC home page
Springer Nature - PMC COVID-19 Collection logoLink to Springer Nature - PMC COVID-19 Collection
. 1993;130(3):269–277. doi: 10.1007/BF01309659

Genetic restriction of murine hepatitis virus type 3 expression in liver and brain: comparative study in BALB/c and C3H mice by immunochemistry and hybridization in situ

D Décimo 1,2, Odile Boespflug 1, M Meunier-Rotival 2, Michelle Hadchouel 2, M Tardieu 1
PMCID: PMC7086966  PMID: 8390822

Summary

To study the host-dependent genetic variations in murine hepatitis virus type 3 (MHV 3) induced diseases, we localized the sites of MHV 3 (Mill Hill strain) expression within liver and brain by immunohistochemistry or hybridization in situ. Two strains of mice were studied: BALB/c mice, which develop an acute and lethal hepatitis and C3H mice which develop a chronic brain infection. In BALB/c mice, viral RNA and antigens appeared during the first 24 h post infection (p.i.) in liver, whereas viral RNA was barely detectable in brain, up until death at day 3 p.i. In C3H mice, viral RNA and antigens were detected simultaneously in liver and brain only at day 2 p.i. In brain, the virus was detected in meningeal and ependymal cells and in perivascular cortical areas (days 5 and 7 p.i.). After day 49, the virus was no longer detected in brain parenchyma, but persisted in meningeal cells. Two host-dependent genetic differences in viral processing were observed in the liver: (1) the virus was first detected in Kupffer cells in BALB/c mice and mostly in hepatocytes in C3H mice; (2) in BALB/c mice, the 180 kDa S viral glycoprotein appeared more frequently cleaved in 90 kDa form than in C3H mice.

Keywords: Hepatitis, Cortical Area, Genetic Difference, Kupffer Cell, Genetic Restriction

References

  • 1.Arnheiter T, Baechi T, Haller O. Adult mouse hepatocytes in primary monolayer culture express genetic resistance to mouse hepatitis virus 3. J Immunol. 1982;129:1275–1281. [PubMed] [Google Scholar]
  • 2.Barthold SW, Smith AL. Mouse hepatitis virus strains: related patterns of tissue tropism in suckling mice. Arch Virol. 1984;81:103–112. doi: 10.1007/BF01309300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Beaufay H, Amar-Costesec A. Cell fractionation techniques. In: Korn ED, editor. Methods in membrane biology, vol 6. New York: Plenum; 1976. pp. 1–100. [Google Scholar]
  • 4.Boespflug O, Godfraind C, Tardieu M. Effect of cyclosporin A on a chronic viral CNS infection in mice. J Neuroimmunol. 1989;21:49–57. doi: 10.1016/0165-5728(89)90158-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Décimo D, Philippe H, Hadchouel M, Tardieu M, Meunier-Rotival M. The gene encoding the nucleocapsid protein: sequence analysis in murine hepatitis virus type 3 and evolution inCoronaviridae. Arch Virol. 1993;130:279–288. doi: 10.1007/BF01309660. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Etiemble J, Moroy T, Jacquemin E, Tiollais P, Buendia MA. Fused transcripts of c-myc and a new cellular locus, hcr in a primary liver tumour. Oncogene. 1989;4:51–57. [PubMed] [Google Scholar]
  • 7.Frana MF, Behnke JN, Sturman LS, Holmes KV. Proteolytic cleavage of the E 2 glycoprotein of murine coronavirus: host dependent differences in proteolytic cleavage and cell fusion. J Virol. 1985;56:912–920. doi: 10.1128/jvi.56.3.912-920.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Jordan CA, Friedrich VL, Godfraind C, Cardellechio CB, Holmes KV, Dubois-Dalcq M. Expression of viral and myelin gene transcripts in a murine CNS demyelinating disease caused by a coronavirus. Glia. 1989;2:318–329. doi: 10.1002/glia.440020505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Lamontagne LM, Dupuy JM. Natural resistance of mice to mouse hepatitis virus type 3 infection is expressed in embryonic fibroblast cells. J Gen Virol. 1984;65:1165–1170. doi: 10.1099/0022-1317-65-7-1165. [DOI] [PubMed] [Google Scholar]
  • 10.Melton DA, Kreig PA, Rebagliati MR, Maniatis T, Zinn K, Green MR. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP 6 promoter. Nucleic Acids Res. 1984;12:7034–7059. doi: 10.1093/nar/12.18.7035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Pereira CA, Steffan AM, Kirn A. Interaction between mouse hepatitis virus and primary cultures of Kupffer and endothelial liver cells from resistant and susceptible inbred mouse strains. J Gen Virol. 1984;65:35–44. doi: 10.1099/0022-1317-65-9-1617. [DOI] [PubMed] [Google Scholar]
  • 12.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]
  • 13.Sorensen O, Dales S. In vivo and in vitro models of demyelinating disease: JHM virus in the rat central nervous system localized by in situ cDNA hybridization and immunofluorescent microscopy. J Virol. 1985;56:434–438. doi: 10.1128/jvi.56.2.434-438.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Sturman LS, Ricard CS, Holmes KV. Proteolytic cleavage of the E 2 glycoprotein of mouse coronavirus: activation of cell-fusing activity of virions by trypsin and separation of two different 90 K cleavage fragments. J Virol. 1985;56:904–911. doi: 10.1128/jvi.56.3.904-911.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Sturman LS, Holmes KV, Behnke J. Isolation of coronavirus envelope glycoproteins and interaction with viral nucleocapsid. J Virol. 1980;33:449–462. doi: 10.1128/jvi.33.1.449-462.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Tardieu M, Goffinet A, Harmant van Rijckevorsel G, Lyon G. Ependymitis, leukoencephalitis, hydrocephalus, and thrombotic vasculitis following chronic infection by mouse hepatitis virus 3 (MHV 3) Acta Neuropathol. 1982;58:168–176. doi: 10.1007/BF00690797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Tardieu M, Boespflug O, Barbé T. Selective tropism of a neurotropic coronavirus for ependymal cells, neurons, and meningeal cells. J Virol. 1986;60:574–582. doi: 10.1128/jvi.60.2.574-582.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Virelizier JL, Virelizier AM, Allison AC. Neuropathological effects of persistent infection of the mice by mouse hepatitis virus. Infect Immunol. 1975;12:1127–1140. doi: 10.1128/iai.12.5.1127-1140.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Virelizier JL, Allison AC. Correlation of persistent mouse hepatitis virus (MHV 3) infection with its effect on mouse macrophage cultures. Arch Virol. 1976;50:279–285. doi: 10.1007/BF01317953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Wege H, Siddell S, Ter Meulen V. The biology and pathogenesis of coronaviruses. Curr Top Microbiol Immunol. 1982;99:165–200. doi: 10.1007/978-3-642-68528-6_5. [DOI] [PubMed] [Google Scholar]
  • 21.Yoshikura H, Tejima S. Role of protease in mouse hepatitis virus-induced cell fusion. Virology. 1981;113:503–511. doi: 10.1016/0042-6822(81)90178-1. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Archives of Virology are provided here courtesy of Nature Publishing Group

RESOURCES