Hemagglutinin-neuraminidase (HN) amino acid alterations in neutralization escape mutants of Kilham mumps virus.
The hemagglutinin-neuraminidase genes of the Kilham strain of mumps virus and three neutralization escape mutants (M11, M12 and M13) of this strain (Löve et al., 1985a) were sequenced using their genomes as template. The predicted amino acid sequences were compared. While one mutant had only one amino acid substitution the other two mutants had four and five respectively. A putative region for the epitope of the selected neutralizing monoclonal antibody was identified in a hydrophilic region encompassing amino acids 352-360, since the single amino acid substitution of one mutant occurred in this region and the other two mutants showed non-conserved amino acid changes in this part of the protein. The previously sequenced prototype strain RW, which lacks capacity to react with the selected neutralizing monoclonal antibody also has one non-conserved amino acid change in the region of the proposed neutralizing epitope. The three mutants showed different biological characteristics. These particular characteristics were therefore interpreted to be primarily associated with strain-specific amino acid changes outside the region of the presumed neutralizing epitope. The decrease in molecular weight in one mutant (M11) was shown to be due to a substitution in position 329 of an asparagine for an aspartic acid, leading to abolishment of a potential N-linked glycosylation site. In the other mutants, one substitution in position 239 of a lysine for a methionine was correlated with an increased neuraminidase activity of strain M12, while a substitution in position 360 of an arginine for a cysteine appeared to represent the most likely explanation for the reduced neurovirulence of strain M13.
Kövamees
J
J
Department of Virology, School of Medicine, Karolinska Institute, Stockholm, Sweden.
Rydbeck
R
R
Orvell
C
C
Norrby
E
E
D000595:Amino Acid Sequence; D004797:Enzyme-Linked Immunosorbent Assay; D006389:Hemagglutinins, Viral / Q000235:genetics*; D008969:Molecular Sequence Data; D009109:Mumps virus / Q000235:genetics*; D009154:Mutation; D009439:Neuraminidase / Q000235:genetics*; D012313:RNA / Q000737:chemistry
D006389:Hemagglutinins, Viral; D012313:RNA; D009439:Neuraminidase