Neurovirulence for Rats of the JHMV Variants Escaped from Neutralization with the S1-Specific Monoclonal Antibodies

  • Fumihiro Taguchi
  • Hideka Suzuki
  • Hiromi Takahashi
  • Hideyuki Kubo
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 380)


We have studied the neurovirulence for rats of the MAb-resistant variants isolated from a highly neurovirulent JHMV, cl-2. The variants, MM6 and MM13, with point mutation located within the N terminal 100 amino acids (aa) of the SI protein showed no alteration in neurovirulence in comparison with cl-2, showing high neurovirulence. The variants, MM65 and MM85, with a deletion composed of about 150 aa located in the middle of the S1 subunit were revealed to be non-neurovirulent. A variant MM78 with one aa deletion, asparagic acid at number 543 from the N terminus of the S1, was shown to be low-virulence. The neurovirulence of these viruses paralleled with the viral growth potential in the rat brain. However, all of these variants as well as parental cl-2 showed high neurovirulence for mice. These results suggest that the domain composed of about 150 aa in the middle of the Sl is critical for high-neurovirulence of JHMV for rats.


Monoclonal Antibody Point Mutation Major Determinant Growth Potential Multiple Site 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Holmes, K.V., E.W., Doller and J.N. Behnke. Analysis of the function of coronavirus glycoprotein by differential inhibition of synthesis with tunicamycin. Adv. Exp. Med. Biol. 1981;142: 133–142PubMedGoogle Scholar
  2. 2.
    Spaan, W., D.Cavanagh, and M.C.Horzinek. Coronaviruses: structure and genome expression. J. Gen. Virol. 1988;69:2939–2952.PubMedCrossRefGoogle Scholar
  3. 3.
    Dalziel, R.G., P.W.Lampert, P.J.Talbot, and M.J.Buchmeier. Site-specific alteration of murine hepatitis virus type 4 peplomer glycoprotein E2 results in reduced neurovirulence. J.Virol. 1986;59: 463– 471.PubMedGoogle Scholar
  4. 4.
    Fleming, J.O., M.D.Trousdale, F.A.K.El-Zaatari, S.A.Stohlman, and L.P. Weiner. Pathogenicity of antigenic variants of murine coronavirus JHM selected with monoclonal antibodies. J.Virol. 1986;58: 869–875.PubMedGoogle Scholar
  5. 5.
    Parker, S.E., T.M. Gallagher, and M.J. Buchmeier. Sequence analysis reveals extensive polymorphism and evidence of deletions within the E2 glycoprotein gene of several strains of murine hepatitis virus. Virology 1989;173:664–673PubMedCrossRefGoogle Scholar
  6. 6.
    Wang, F.-L, J.O. Fleming and M.M.C. Lai Sequence analysis of the spike protein gene of murine coronavirus variants: Study of genetic sites affecting neuropathogenicity. Virology 1992; 186: 742–7491.PubMedCrossRefGoogle Scholar
  7. 7.
    Taguchi, F., S.G.Siddell, H.Wege, and V.ter Meulen. Characterization of a variant virus selected in rat brain after infection by coronavirus mouse hepatitis virus JHM. J. Virol. 1985;54: 429–435.PubMedGoogle Scholar
  8. 8.
    Matsubara, Y., R.Watanabe, and F.Taguchi. Neurovirulence of six different murine coronavirus JHMV variants for rats. Virus Res. 1991;20: 45–58.PubMedCrossRefGoogle Scholar
  9. 9.
    Kubo, H., S.Y.Takase, and F.Taguchi. Neutralization and fusion inhibition activities of monoclonal antibodies specific for the S1 subunit of the spike protein of neurovirulent murine coronavirus JHMV cl-2 variant. J. Gen. Virol. 1993;74: 1421–1425.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Fumihiro Taguchi
    • 1
  • Hideka Suzuki
    • 1
  • Hiromi Takahashi
    • 1
  • Hideyuki Kubo
    • 1
  1. 1.NCNPNational Institute of NeuroscienceKodaira TokyoJapan

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