Amino acid substitutions and an insertion in the spike glycoprotein extend the host range of the murine coronavirus MHV-A59

Larissa B. Thackray, Kathryn V. Holmes

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

The murine coronavirus [murine hepatitis virus (MHV)] is limited to infection of susceptible mice and murine cell lines by the specificity of the spike glycoprotein (S) for its receptor, murine carcinoembryonic antigen cell adhesion molecule 1a (mCEACAM1a). We have recently shown that 21 aa substitutions and a 7-aa insert in the N-terminal region of S are associated with the extended host range of a virus variant derived from murine cells persistently infected with the A59 strain of MHV (MHV-A59). We used targeted RNA recombination (TRR) to generate isogenic viruses that differ from MHV-A59 by the 21 aa substitutions or the 7-aa insert in S. Only viruses with both the 21 aa substitutions and the 7-aa insert in S infected hamster, feline, and monkey cells. These viruses also infected murine cells in the presence of blocking anti-mCEACAM1a antibodies. Thus, relatively few changes in the N-terminal region of S1 are sufficient to permit MHV-A59 to interact with alternative receptors on murine and non-murine cells.

Original languageEnglish
Pages (from-to)510-524
Number of pages15
JournalVirology
Volume324
Issue number2
DOIs
StatePublished - Jul 1 2004

Keywords

  • Extended host range
  • Murine coronavirus
  • Persistent infection
  • Receptor jumping mutants
  • Spike glycoprotein
  • Targeted RNA recombination

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