Functional chimeric HN glycoproteins derived from Newcastle disease virus and human parainfluenza virus-3.
Newcastle disease virus (NDV) is primarily a respiratory tract pathogen of birds, particularly chickens, but it occasionally produces infection in man. Human parainfluenza virus type 3 (hPIV3) is a common respiratory pathogen, particularly in young children. These two viruses gain entry to host cells via direct fusion between the viral envelope and the cell membrane, mediated by the two surface glycoproteins: the hemagglutinin-neuraminidase (HN) and fusion (F) proteins. Promotion of fusion by HN and F requires that they are derived from homologous viruses. We have constructed chimeric proteins composed of domains from heterologous 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 was found to segregate with a segment extending from the middle of the transmembrane anchor to the top of the putative stalk region of the ectodomain. All of the chimeras, in which the globular domain is derived from the NDV HN and various lengths of the stalk region are derived from the hPIV3 HN maintain receptor binding activity, but some have markedly 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 the globular domain of the HN protein spike.
Deng
R
R
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, USA.
Mirza
A M
AM
Mahon
P J
PJ
Iorio
R M
RM
D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000737:chemistry; D001665:Binding Sites; D002460:Cell Line; D006224:Cricetinae; D015707:HN Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008561:Membrane Fusion; D008969:Molecular Sequence Data; D009522:Newcastle disease virus / Q000378:metabolism*; D010224:Parainfluenza Virus 3, Human / Q000378:metabolism*; D010449:Peptide Mapping; D017510:Protein Folding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014760:Viral Fusion Proteins / Q000235:genetics / Q000378:metabolism
D000956:Antigens, Viral; D015707:HN Protein; D011993:Recombinant Fusion Proteins; D014760:Viral Fusion Proteins