Mutated form of the Newcastle disease virus hemagglutinin-neuraminidase interacts with the homologous fusion protein despite deficiencies in both receptor recognition and fusion promotion.
The Newcastle disease virus (NDV) hemagglutinin-neuraminidase (HN) protein mediates attachment to cellular receptors. The fusion (F) protein promotes viral entry and spread. However, fusion is dependent on a virus-specific interaction between the two proteins that can be detected at the cell surface by a coimmunoprecipitation assay. A point mutation of I175E in the neuraminidase (NA) active site converts the HN of the Australia-Victoria isolate of the virus to a form that can interact with the F protein despite negligible receptor recognition and fusion-promoting activities. Thus, I175E-HN could represent a fusion intermediate in which HN and F are associated and primed for the promotion of fusion. Both the attachment and fusion-promoting activities of this mutant HN protein can be rescued either by NA activity contributed by another HN protein or by a set of four substitutions at the dimer interface. These substitutions were identified by the evaluation of chimeras composed of segments from HN proteins derived from two different NDV strains. These findings suggest that the I175E substitution converts HN to an F-interactive form, but it is one for which receptor binding is still required for fusion promotion. The data also indicate that the integrity of the HN dimer interface is critical to its receptor recognition activity.
Li
Jianrong
J
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655-0122, USA.
Quinlan
Edward
E
Mirza
Anne
A
Iorio
Ronald M
RM
D000595:Amino Acid Sequence; D000818:Animals; D006224:Cricetinae; D015707:HN Protein / Q000737:chemistry / Q000502:physiology*; D008561:Membrane Fusion; D008969:Molecular Sequence Data; D009154:Mutation; D009522:Newcastle disease virus / Q000502:physiology*; D011991:Receptors, Virus / Q000502:physiology; D014760:Viral Fusion Proteins / Q000502:physiology*
D015707:HN Protein; D011991:Receptors, Virus; D014760:Viral Fusion Proteins