The C12 mutant of MHV-A59 is very weakly demyelinating and has five amino acid substitutions restricted to the spike and replicase genes.
C12, an attenuated, fusion defective, very weakly hepatotropic mutant of MHV-A59 has been further characterized. 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 minimal demyelination. Thus acute encephalitis is not sufficient for induction of demyelination by wild type MHV-A59. We have previously shown that C12 has two amino acid substitutions relative to wild type virus in the spike gene, Q159L (in the receptor binding domain of S1) and H716D (in the signal sequence for cleavage of S). We have now sequenced the rest of the 31 kb genome of C12 and compared it to wild type virus. Only three additional amino acids substitutions were found, all within the replicase gene, one in the predicted papain like proteinase (PLP)-2 domain and one in the predicted helicase domain. Thus, determinants of virulence, hepatotropism, and demyelination may map to the replicase gene as well as to the spike gene.
Department of Microbiology, University of Pennsylvania, Philadelphia 19104, USA.
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Leparc-Goffart
S T
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Hingley
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Jiang
M M
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Chua
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Lavi
S R
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Weiss
D019943:Amino Acid Substitution; D000818:Animals; D003711:Demyelinating Diseases; D016679:Genome, Viral; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D006517:Murine hepatitis virus / Q000235:genetics* / Q000502:physiology; D009154:Mutation; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics*; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins / Q000235:genetics*
D008562:Membrane Glycoproteins; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; D012324:RNA-Dependent RNA Polymerase