Functional properties and genetic relatedness of the fusion and hemagglutinin-neuraminidase proteins of a mumps virus-like bat virus.
A bat virus with high phylogenetic relatedness to human mumps virus (MuV) was identified recently at the nucleic acid level. We analyzed the functional activities of the hemagglutinin-neuraminidase (HN) and the fusion (F) proteins of the bat virus (batMuV) and compared them to the respective proteins of a human isolate. Transfected cells expressing the F and HN proteins of batMuV were recognized by antibodies directed against these proteins of human MuV, indicating that both viruses are serologically related. Fusion, hemadsorption, and neuraminidase activities were demonstrated for batMuV, and either bat-derived protein could substitute for its human MuV counterpart in inducing syncytium formation when coexpressed in different mammalian cell lines, including chiropteran cells. Cells expressing batMuV glycoproteins were shown to have lower neuraminidase activity. The syncytia were smaller, and they were present in lower numbers than those observed after coexpression of the corresponding glycoproteins of a clinical isolate of MuV (hMuV). The phenotypic differences in the neuraminidase and fusion activity between the glycoproteins of batMuV and hMuV are explained by differences in the expression level of the HN and F proteins of the two viruses. In the case of the F protein, analysis of chimeric proteins revealed that the signal peptide of the bat MuV fusion protein is responsible for the lower surface expression. These results indicate that the surface glycoproteins of batMuV are serologically and functionally related to those of hMuV, raising the possibility of bats as a reservoir for interspecies transmission.


OBJECTIVE
The recently described MuV-like bat virus is unique among other recently identified human-like bat-associated viruses because of its high sequence homology (approximately 90% in most genes) to its human counterpart. Although it is not known if humans can be infected by batMuV, the antigenic relatedness between the bat and human forms of the virus suggests that humans carrying neutralizing antibodies against MuV are protected from infection by batMuV. The close functional relationship between MuV and batMuV is demonstrated by cooperation of the respective HN and F proteins to induce syncytium formation in heterologous expression studies. An interesting feature of the glycoproteins of batMuV is the downregulation of the fusion activity by the signal peptide of F, which has not been reported for other paramyxoviruses. These results are important contributions for risk assessment and for a better understanding of the replication strategy of batMuV.
Institute of Virology, University of Veterinary Medicine Hannover, Hannover, Germany.
Nadine
N
Krüger
Institute of Virology, University of Veterinary Medicine Hannover, Hannover, Germany.
Markus
M
Hoffmann
Institute of Virology, University of Bonn Medical Centre, Bonn, Germany.
Jan Felix
JF
Drexler
Institute of Virology, University of Bonn Medical Centre, Bonn, Germany.
Marcel Alexander
MA
Müller
Institute of Virology, University of Bonn Medical Centre, Bonn, Germany.
Victor Max
VM
Corman
Division of Viral Products, Center for Biologics Evaluation and Research, FDA, Bethesda, Maryland, USA.
Christian
C
Sauder
Division of Viral Products, Center for Biologics Evaluation and Research, FDA, Bethesda, Maryland, USA.
Steven
S
Rubin
Department of Infectious Diseases, University of Georgia, Athens, Georgia, USA.
Biao
B
He
Division of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
Claes
C
Örvell
Institute of Virology, University of Bonn Medical Centre, Bonn, Germany.
Christian
C
Drosten
Institute of Virology, University of Veterinary Medicine Hannover, Hannover, Germany Georg.Herrler@tiho-hannover.de.
Georg
G
Herrler
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D001483:Base Sequence; D002685:Chiroptera / Q000821:virology*; D002522:Chlorocebus aethiops; D017931:DNA Primers / Q000235:genetics; D005434:Flow Cytometry; D015967:Gene Expression Regulation, Viral / Q000235:genetics*; D015726:Giant Cells / Q000378:metabolism; D015707:HN Protein / Q000235:genetics* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009109:Mumps virus / Q000201:enzymology* / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D014709:Vero Cells; D014760:Viral Fusion Proteins / Q000235:genetics* / Q000378:metabolism
D000914:Antibodies, Viral; D017931:DNA Primers; D015707:HN Protein; D014760:Viral Fusion Proteins