Hepatitis Mutants of Mouse Hepatitis Virus Strain A59

  • S. T. Hingley
  • J. L. Gombold
  • E. Lavi
  • S. R. Weiss
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 380)


MHV-A59 causes acute meningoencephalitis and hepatitis in susceptible mice, and a persistent productive, but nonlytic, infection of cultured glial cells. We have shown previously that viruses isolated from persistently infected glial cell cultures have a fusion-defective phenotype and were impaired in their abilities to cause hepatitis compared to wild-type MHV-A59. Two mutants chosen for detailed study, B11 and C12, display two distinct hepatitis phenotypes. The ability of B11 to replicate in the liver was dependent on infectious dose and route of inoculation, while C12 consistently displayed decreased liver titers regardless of dose and route of inoculation. Sequence analysis of wild-type, mutant and revertant S proteins indicates that 1) a mutation in the N terminal subunit of S, resulting in a glutamine to leucine amino acid substitution (Q159L), may affect ability to cause hepatitis and 2) a cleavage site mutation (H716D) which determines fusogenicity is not responsible for the altered hepatitis phenotype. Sequence analysis indicated that hepatitis-producing revertants did not revert at mutation Q159L, although it is possible that a mutation in the heptad repeat domain of S2 may compensate for the mutation in S1. Since Bll, C12 and a nonattenuated fusion mutant (B12) have identical S protein sequences, there must be additional mutations outside of S which influence both virulence and ability to replicate in the liver.


Mouse Fibroblast Cell Susceptible Mouse Mouse Hepatitis Virus Fusion Mutant Murine Coronavirus 
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  1. 1.
    Gombold, J.L., Hingley, S.T., Weiss, S.R. Fusion-defective mutants of mouse hepatits virus A59 contain a mutation in the spike protein cleavage signal. J Virol 1993;67:4504–4512.PubMedGoogle Scholar
  2. 2.
    Hingley, S.T., Gombold, J.L., Lavi, E., Weiss, S.R. MHV-A59 fusion mutants are attenuated and display altered hepatotropism. Virology 1994;200:1–10.PubMedCrossRefGoogle Scholar
  3. 3.
    Dveksler,G.S., Dieffenbach, C.W., Cardellichio, C.B., McCuaig,K., Pensiero, M.N., Jiang, G.-S., Beauchemin, N., Holmes, K.V. Several members of the mouse carcinoembryonic antigen-related glycoprotein family are functional receptors for the coronavirus mouse hepatitis virus-A59. J Virol 1993;67: 1 -8.PubMedGoogle Scholar
  4. 4.
    Williams, R.K., Jiang, G.-S., Holmes, K.V. Receptor for mouse hepatitis virus is a member of the carcinoembryonic antigen family of glycoproteins. Proc Natl Acad Sci USA 1991;88:5533–5536.PubMedCrossRefGoogle Scholar
  5. 5.
    Daniel, C, Anderson, R., Buchmeier, M.J., Fleming, J.O., Spaan, W.J.M., Wege, H., Talbot, P.J. Identification of an immunodominant linear neutralization domain on the S2 portion of the murine coronavirus spike glycoprotein and evidence that it forms part of a complex tridimensional structure. J Virol 1993;67:1185–1194.PubMedGoogle Scholar
  6. 6.
    Wege, H., Dorries,R. Wege, H. Hybridoma antibodies to the murine coronavirus JHM: characterization of epitopes on the peplomer protein (E2). J Gen Virol 1984;65:1931–1942.PubMedCrossRefGoogle Scholar
  7. 7.
    Grosse, B., Siddell, S.G. Single amino acid changes in the S2 subunit of the MHV surface glycoprotein confer resistence to neutralization by S1 subunit-specific monoclonal antibody. Virology 1994;202:814–824.PubMedCrossRefGoogle Scholar
  8. 8.
    Wang, F.I., Fleming, J.O., Lai, M.M.C. Sequence analysis of the spike protein gene of murine coronavirus variants: study of genetic sites affecting neuropathogenicity. Virology 1992;186:742–749.PubMedCrossRefGoogle Scholar
  9. 9.
    Koetzner, C.A., Parker M.M., Ricard, C.S., Sturman, L.S., Masters, P.S. Repair and mutagenesis of the genome of a deletion mutant of the coronavirus mouse hepatitis virus by targented RNA recombination. J Virol 1992;66:1841–1848.PubMedGoogle Scholar
  10. 10.
    van der Most, R.G., Heijnen, L., Spaan, W.J.M., de Groot R.J. Homologous RNA recombination allows efficient introduction of site -specific mutation into the genome of coronavirus MHV-A59 via synthetic co-replicating RNAs. Nucleic Acids Res 1992;20:3375–3381.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • S. T. Hingley
    • 1
  • J. L. Gombold
    • 2
  • E. Lavi
    • 3
  • S. R. Weiss
    • 4
  1. 1.Department of Microbiology and ImmunologyPhiladelphia College of Osteopathic MedicinePhiladelphiaUSA
  2. 2.Department of Microbiology and ImmunologyLouisiana State University Medical CenterShreveportUSA
  3. 3.Department of PathologyUniversity of PennsylvaniaPhiladelphiaUSA
  4. 4.Department of MicrobiologyUniversity of PennsylvaniaPhiladelphiaUSA

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