Site-specific alteration of murine hepatitis virus type 4 peplomer glycoprotein E2 results in reduced neurovirulence

Robert Dalziel, P W Lampert, Pierre J Talbot, M J Buchmeier

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Strains of the murine coronavirus mouse hepatitis virus type 4 (MHV-4) which contained a mutation in the E2 peplomer glycoprotein were obtained by selection for resistance to neutralization by monoclonal antibodies. Characterization of six variants representing two independent epitopes on E2, E2B and E2C, by in vitro neutralization and antibody-binding assays demonstrated that selection for an alteration in epitope E2B also resulted in changes in epitope E2C and vice versa. We observed a mutation frequency of approximately 10(-4.3) to 10(-4.6), which is consistent with the expected occurrence of single point mutations. The variant virus strains were attenuated with respect to neurovirulence when compared with wild-type MHV-4. Mice normally develop encephalomyelitis and die after wild-type MHV-4 infection. Mice receiving 2- to 3-log-higher doses of the variant strains survived and developed demyelinating disease. As the disease progressed, evidence of remyelination and ongoing demyelination was observed up to 65 days after infection. Virus reisolated 15 days after infection retained the variant phenotype. The data indicate that the E2 glycoprotein plays a central role in determining the cellular tropism and virulence of MHV-4 in the mouse.
Original languageEnglish
Pages (from-to)463-71
Number of pages9
JournalJournal of Virology
Volume59
Issue number2
Publication statusPublished - Aug 1986

Keywords / Materials (for Non-textual outputs)

  • Animals
  • Antibodies, Monoclonal/diagnostic use
  • Brain/microbiology
  • Demyelinating Diseases/microbiology
  • Demyelinating Diseases/pathology
  • Encephalitis/microbiology
  • Glycoproteins/genetics
  • Glycoproteins/immunology
  • Hepatitis, Viral, Animal/microbiology
  • Hepatitis, Viral, Animal/pathology
  • Liver/microbiology
  • Mice
  • Murine hepatitis virus/genetics
  • Murine hepatitis virus/pathogenicity
  • Neutralization Tests
  • Viral Proteins/genetics
  • Viral Proteins/immunology

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