Key result
Sequencing links HN and F protein amino acid differences to non-neurovirulent mumps virus phenotypes.
Why the study?
The molecular differences underlying neurovirulence in mumps virus strains were not fully characterized during the 1998-2000 Lithuania epidemic.
Specific amino acid substitutions in the HN and F proteins of mumps virus strains may play a role in determining the neurovirulent phenotype.
May guide mumps strain attenuation research; animal data leave open human neurovirulence relevance.
Mumps virus strains isolated during an epidemic in Lithuania in 1998 - 2000 were studied. Viruses of the neurovirulent C1 and non-neurovirulent C2 small hydrophobic (SH) genotype variant were sequenced for the haemagglutinin-neuraminidase (HN) and fusion (F) protein genes. Amino acid differences between C1 and C2 strains were found for both proteins. Two amino acid differences were of potential importance for the non-neurovirulent phenotype of the C2 virus. Four of 5 C2 strains exhibited the amino acid arginine instead of lysine at position 335 of the HN protein, and the amino acid phenylalanine was found instead of serine at amino acid position 195 of the F protein. Amino acid differences at these positions have previously been reported to associate with a change in neurovirulence and fusion activity. In addition, the HN gene of the neurovirulent Kilham strain of genotype A was sequenced. The deduced amino acid sequence showed different amino acids compared to both genotypes A and C on some positions. Notably, amino acid differences located in previously identified neutralizing epitopes were found at positions 266, 354 and 356 of the HN protein compared to other genotype A strains. The amino acid differences between Kilham virus strain and other genotype A strains and the similarity of the Kilham HN protein (7 positions) to neurovirulent genotype C strains on some amino acid positions may indicate a possible role for this protein in mumps virus neurovirulence.
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Rafiefard et al. (2005) studied Mumps virus infection. Neurovirulent C1 and non-neurovirulent C2 small hydrophobic (SH) genotype variant strains vs. Other genotype A strains was evaluated on Amino acid differences in haemagglutinin-neuraminidase (HN) and fusion (F) protein genes. Amino acid differences between neurovirulent C1 and non-neurovirulent C2 mumps virus strains were identified in the HN and F proteins, potentially explaining the non-neurovirulent phenotype.
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