Recombinant mumps viruses expressing the batMuV fusion glycoprotein are highly fusion active and neurovirulent

J Gen Virol. 2016 Nov;97(11):2837-2848. doi: 10.1099/jgv.0.000596. Epub 2016 Sep 2.

Abstract

A recent study reported the detection of a bat-derived virus (BatPV/Epo_spe/AR1/DCR/2009, batMuV) with phylogenetic relatedness to human mumps virus (hMuV). Since all efforts to isolate infectious batMuV have reportedly failed, we generated recombinant mumps viruses (rMuVs) in which the open reading frames (ORFs) of the fusion (F) and haemagglutinin-neuraminidase (HN) glycoproteins of an hMuV strain were replaced by the corresponding ORFs of batMuV. The batMuV F and HN proteins were successfully incorporated into viral particles and the resultant chimeric virus was able to mediate infection of Vero cells. Distinct differences were observed between the fusogenicity of rMuVs expressing one or both batMuV glycoproteins: viruses expressing batMuV F were highly fusogenic, regardless of the origin of HN. In contrast, rMuVs expressing human F and bat-derived HN proteins were less fusogenic compared to hMuV. The growth kinetics of chimeric MuVs expressing batMuV HN in combination with either hMuV or batMuV F were similar to that of the backbone virus, whereas a delay in virus replication was obtained for rMuVs harbouring batMuV F and hMuV HN. Replacement of the hMuV F and HN genes or the HN gene alone by the corresponding batMuV genes led to a slight reduction in neurovirulence of the highly neurovirulent backbone strain. Neutralizing antibodies inhibited infection mediated by all recombinant viruses generated. Furthermore, group IV anti-MuV antibodies inhibited the neuraminidase activity of bat-derived HN. Our study reports the successful generation of chimeric MuVs expressing the F and HN proteins of batMuV, providing a means for further examination of this novel batMuV.

MeSH terms

  • Animals
  • Antibodies, Viral / immunology
  • Brain / immunology
  • Brain / virology*
  • Chiroptera / virology*
  • Female
  • Gene Expression
  • HN Protein / administration & dosage
  • HN Protein / genetics
  • HN Protein / immunology*
  • Humans
  • Male
  • Mumps / immunology*
  • Mumps / prevention & control
  • Mumps / virology
  • Mumps virus / classification
  • Mumps virus / genetics
  • Mumps virus / immunology*
  • Mumps virus / pathogenicity
  • Rats
  • Rats, Inbred Lew
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Viral Fusion Proteins / administration & dosage
  • Viral Fusion Proteins / genetics
  • Viral Fusion Proteins / immunology*
  • Virulence

Substances

  • Antibodies, Viral
  • HN Protein
  • Recombinant Fusion Proteins
  • Viral Fusion Proteins