Amino Acid Substitutions in Matrix, Fusion and Hemagglutinin Proteins of Wild Measles Virus for Adaptation to Vero Cells

Abstract

Background: Wild-type measles virus (MV) is isolated in B95a but not in Vero cells. Through an adaptation process of wild-type MV to Vero cells, several amino acid substitutions were reported. Methods: Six strains were adapted to Vero cells and membrane (M), fusion (F) and hemagglutinin (H) genes were sequenced. Cell fusion was assessed and recombinant MVs were constructed, having wild-type H or M gene with or without mutations. Results: No F gene substitution was noted. Amino-acid substitutions at positions 481 from Asn to Tyr (N481Y) and 546 from Ser to Gly (S546G) were observed in the H protein. Glu at position 89 of the M protein was substituted for Gly (E89G) and two mutations were noted at positions 62 (S62R) and 83 (S83P) in M protein. Recombinant viruses with mutation(s) detected in Vero-adapted strains induced a cytopathic effect and grew well in Vero cells, but those with the wild type did not. Recombinant viruses with mutation(s) demonstrated lower viral growth in B95a cells. Conclusions: Substitutions of E89G, S62R and S83P of the M protein were newly observed through adaptation to Vero cells, besides the mutations described in previous reports, with varying adaptation for each strain.