FUNCTIONAL CHIMERIC HN GLYCOPROTEINS DERIVED FROM NEWCASTLE-DISEASE VIRUS AND HUMAN PARAINFLUENZA VIRUS-3

Newcastle disease virus (NDV) is primarily a respiratory tract pathoge n of birds, particularly chickens, but it occasionally produces infect ion in man. Human parainfluenza virus type 3 (hPIV3) is a common respi ratory pathogen, particularly in young children. These two viruses gai n entry to host cells via direct fusion between the viral envelope and the cell membrane, mediated by the two surface glycoproteins: the hem agglutinin-neuraminidase (HN) and fusion (F) proteins. Promotion of fu sion by HN and F requires that they are derived from homologous viruse s. We have constructed chimeric proteins composed of domains from hete rologous HN proteins. Their ability to bind cellular receptors and to complement the F protein of each virus in the promotion of fusion were evaluated in a transient expression system. The fusion specificity wa s found to segregate with a segment extending from the middle of the t ransmembrane anchor to the top of the putative stalk region of the ect odomain. All of the chimeras, in which the globular domain is derived from the NDV HN and various lengths of the stalk region are derived fr om the hPIV3 HN maintain receptor binding activity, but some have mark edly reduced neuraminidase (NA) activity. Decrease in the NA activity of the chimeras correlates with alteration in the antigenic structure of the globular domain. This suggests that the stalk region of the HN spike is important for maintenance of the structure and function of th e globular domain of the HN protein spike.