title: Altered pathogenesis of a mutant of the murine coronavirus MHV-A59 is associated with a Q159L amino acid substitution in the spike protein.
abstract: C12, an attenuated, fusion delayed, very weakly hepatotropic mutant of mouse hepatitis virus strain A59 (MHV-A59( has been further characterized. We have previously shown that C12 has two amino acid substitutions relative to wild type virus in the spike protein, Q159L (within a region of S1 shown to bind to viral receptor in an in vitro assay) and H716D (in the proteolytic cleavage recognition site). We have sequenced the rest of the 31-kb genome of C-12 and compared it to wild type virus. Only three additional amino acids substitutions were found, all encoded within the replicase gene. Analysis of C12 in vivo in C57Bl/6 mice has shown that despite the fact that this virus replicates in the brain to titers at least as high as wild type and causes acute encephalitis similar to wild-type, this virus causes a minimal level of demyelination and only at very high levels of virus inoculation. Thus acute encephalitis is not sufficient for the induction of demyelination by MHV-A59. Analysis of mutants isolated at earlier times from the same persistently infected glial cell culture as C12, as well as mutants isolated from a second independent culture of persistently infected glial cells, suggests that both the weakly demyelinating and the weakly hepatotropic phenotypes of C12 are associated with the Q159L amino acid substitution.
authors.affiliation: Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
authors.forename: I
authors.initials: I
authors.lastname: Leparc-Goffart
authors.forename: S T
authors.initials: ST
authors.lastname: Hingley
authors.forename: M M
authors.initials: MM
authors.lastname: Chua
authors.forename: X
authors.initials: X
authors.lastname: Jiang
authors.forename: E
authors.initials: E
authors.lastname: Lavi
authors.forename: S R
authors.initials: SR
authors.lastname: Weiss
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D018352:Coronavirus Infections / Q000821:virology*; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D006517:Murine hepatitis virus / Q000235:genetics* / Q000472:pathogenicity*; D009154:Mutation; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins / Q000235:genetics*; D014774:Virulence / Q000235:genetics
chemical_list: D008562:Membrane Glycoproteins; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins