Characterization of genotype-specific epitopes of the HN protein of mumps virus

C Orvell1, A R Alsheikhly, M Kalantari

  • 1Huddinge University Hospital, Department of Clinical Virology, Karolinska Institute, Sweden. clor@vird01.hs.sll.se

Insights

Mumps virus genotype A was studied using monoclonal antibodies targeting the HN protein. Escape mutants showed amino acid changes, but these changes did not explain genotype-specific neutralization differences.

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Mumps virus exhibits genetic diversity with multiple genotypes.
  • The haemagglutinin-neuraminidase (HN) protein is crucial for mumps virus infectivity and is a target for neutralizing antibodies.

Purpose of the Study:

  • To investigate the antigenic properties of the mumps virus HN protein.
  • To analyze mutations in the HN gene of neutralization-escape mutants.
  • To explore genotype-specific neutralization responses.

Main Methods:

  • Culturing mumps virus (SBL-1 strain, genotype A) with monoclonal antibodies against the HN protein.
  • Sequencing the HN genes of neutralization-escape mutants.
  • Comparing amino acid sequences of parental and mutant viruses.
  • Testing monoclonal antibody reactivity against various mumps virus strains (genotypes C and D).
  • Assessing type-specific neutralization antibody responses in rabbits.

Main Results:

  • Monoclonal antibodies targeting the HN protein inhibited viral activity.
  • Amino acid substitutions at positions 269, 352, and 354 were identified in escape mutants.
  • These specific monoclonal antibodies did not react with genotype C or D strains.
  • Type-specific neutralization responses were observed for genotypes A and D, but not consistently reflected in HN protein sequence differences.

Conclusions:

  • The study identified specific amino acid changes in the HN protein associated with escape from monoclonal antibody neutralization.
  • Significant antigenic differences exist between mumps virus genotypes, impacting neutralization.
  • Further research is required to assess the effectiveness of mumps virus vaccines against different genotypes.