Altered pathogenesis of a mutant of the murine coronavirus MHV-A59 is associated with a Q159L amino acid substitution in the spike protein.
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.
Leparc-Goffart
I
I
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Hingley
S T
ST
Chua
M M
MM
Jiang
X
X
Lavi
E
E
Weiss
S R
SR
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
D008562:Membrane Glycoproteins; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins