Mutations in the Newcastle disease virus hemagglutinin-neuraminidase protein that interfere with its ability to interact with the homologous F protein in the promotion of fusion.
Recent evidence suggests that the attachment (HN) and fusion (F) glycoproteins of Newcastle disease virus interact at the cell surface in a virus-specific manner to promote syncytium formation. Consistent with the existence of such an interaction, we have shown that it is possible to coimmunoprecipitate (co-IP) the two proteins from the surface of transiently expressing cells using a monoclonal antibody to either protein. Further, we show that a point mutation in the globular domain of HN that abolishes its receptor recognition and neuraminidase (NA) and fusion activities also abolishes its ability to interact with F in the co-IP assay. The mechanism by which this mutation might interfere with the interaction between the two proteins is discussed in terms of the postulate that recognition by HN of cellular receptors triggers its interaction with F and the apparently conflicting evidence for an interaction between the two proteins in the endoplasmic reticulum. Also, characterization of a set of chimeric HN proteins, having short overlapping sequences from a heterologous HN protein in the F-specific domain in the protein stalk, reveals that a weakened interaction between HN and F is still sufficient to trigger fusion.
Deng
R
R
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, Massachusetts, 01655-0122, USA.
Wang
Z
Z
Mahon
P J
PJ
Marinello
M
M
Mirza
A
A
Iorio
R M
RM
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015153:Blotting, Western; D002460:Cell Line; D006224:Cricetinae; D017930:Genes, Reporter; D015707:HN Protein / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009522:Newcastle disease virus; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics; D014760:Viral Fusion Proteins / Q000235:genetics* / Q000276:immunology
D000911:Antibodies, Monoclonal; D015707:HN Protein; D011993:Recombinant Fusion Proteins; D014760:Viral Fusion Proteins