Functional Properties and Genetic Relatedness of the Fusion and Hemagglutinin-Neuraminidase Proteins of a Mumps Virus-Like Bat Virus

被引:12
作者
Krueger, Nadine [1 ]
Hoffmann, Markus [1 ]
Drexler, Jan Felix [2 ]
Mueller, Marcel Alexander [2 ]
Corman, Victor Max [2 ]
Sauder, Christian [3 ]
Rubin, Steven [3 ]
He, Biao [4 ]
Orvell, Claes [5 ]
Drosten, Christian [2 ]
Herrler, Georg [1 ]
机构
[1] Univ Vet Med Hannover, Inst Virol, Hannover, Germany
[2] Univ Bonn, Med Ctr, Inst Virol, Bonn, Germany
[3] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA
[4] Univ Georgia, Dept Infect Dis, Athens, GA 30602 USA
[5] Karolinska Inst, Div Lab Med, Stockholm, Sweden
关键词
SARS-LIKE CORONAVIRUS; SURFACE GLYCOPROTEINS; SH GENE; INFLUENZA; HENIPAVIRUS; SEQUENCE; ENTRY; PARAMYXOVIRUSES; ALIGNMENT; GENOTYPES;
D O I
10.1128/JVI.03693-14
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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. IMPORTANCE 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.
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收藏
页码:4539 / 4548
页数:10
相关论文
共 47 条
[1]   Clustering of mumps virus isolates by SH gene sequence only partially reflects geographical origin [J].
Afzal, MA ;
Buchanan, J ;
Heath, AB ;
Minor, PD .
ARCHIVES OF VIROLOGY, 1997, 142 (02) :227-238
[2]  
[Anonymous], 2012, Wkly Epidemiol Rec, V87, P217
[3]  
Atkinson WM, 2012, EPIDEMIOLOGY PREVENT
[4]   QUANTITATIVE MEASUREMENT OF PARAMYXOVIRUS FUSION - DIFFERENCES IN REQUIREMENTS OF GLYCOPROTEINS BETWEEN SIMIAN-VIRUS-5 AND HUMAN PARAINFLUENZA-VIRUS-3 OR NEWCASTLE-DISEASE VIRUS [J].
BAGAI, S ;
LAMB, RA .
JOURNAL OF VIROLOGY, 1995, 69 (11) :6712-6719
[5]  
BEARD CM, 1977, MAYO CLIN PROC, V52, P3
[6]   Synthetic recombinant bat SARS-like coronavirus is infectious in cultured cells and in mice [J].
Becker, Michelle M. ;
Graham, Rachel L. ;
Donaldson, Eric F. ;
Rockx, Barry ;
Sims, Amy C. ;
Sheahan, Timothy ;
Pickles, Raymond J. ;
Corti, Davide ;
Johnston, Robert E. ;
Baric, Ralph S. ;
Denison, Mark R. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (50) :19944-19949
[7]   MUMPS .2. VIRUS HAEMAGGLUTINATION AND SEROLOGICAL REACTIONS [J].
BEVERIDGE, WIB ;
LIND, PE .
AUSTRALIAN JOURNAL OF EXPERIMENTAL BIOLOGY AND MEDICAL SCIENCE, 1946, 24 (02) :127-132
[8]   Type I Interferon Reaction to Viral Infection in Interferon-Competent, Immortalized Cell Lines from the African Fruit Bat Eidolon helvum [J].
Biesold, Susanne E. ;
Ritz, Daniel ;
Gloza-Rausch, Florian ;
Wollny, Robert ;
Drexler, Jan Felix ;
Corman, Victor M. ;
Kalko, Elisabeth K. V. ;
Oppong, Samuel ;
Drosten, Christian ;
Mueller, Marcel A. .
PLOS ONE, 2011, 6 (11)
[9]   COMPARISON OF NEURAMINIDASES OF PARAMYXOVIRUSES WITH IMMUNOLOGICALLY DISSIMILAR HEMAGGLUTININS [J].
BROSTROM, MA ;
BRUENING, G ;
BANKOWSKI, RA .
VIROLOGY, 1971, 46 (03) :856-+
[10]  
BURNET F M, 1945, Aust J Exp Biol Med Sci, V23, P189