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) glycoprote ins of Newcastle disease virus interact at the cell surface in a virus-spec ific manner to promote syncytium formation. Consistent with the existence o f such an interaction, we have shown that it is possible to coimmunoprecipi tate (co-IP) the two proteins from the surface of transiently expressing ce lls using a monoclonal antibody to either protein. Further, we show that a point mutation in the globular domain of HN that abolishes its receptor rec ognition and neuraminidase (NA) and fusion activities also abolishes its ab ility to interact with F in the co-IP assay. The mechanism by which this mu tation might interfere with the interaction between the two proteins is dis cussed in terms of the postulate that recognition by HN of cellular recepto rs triggers its interaction with F and the apparently conflicting evidence for an interaction between the two proteins in the endoplasmic reticulum. A lso, characterization of a set of chimeric HN proteins, having short overla pping 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. (C) 1999 Academic Press.