A single amino acid substitution in the hemagglutinin-neuraminidase of Newcastle disease virus results in a protein deficient in both functions.

Sequence determinations of the hemagglutinin-neuraminidase (HN) glycoproteins of a temperature-sensitive mutant of Newcastle disease virus and two sequentially selected revertants had previously shown that substitution at a pair of residues, 129 and 175, resulted in a deficiency in neuraminidase (NA) activity, which was partially restored by a third substitution at residue 193. To evaluate the role of the substitution at residue 175 in diminished NA activity, the mutation was introduced into HN and the protein expressed in COS cells. The mutated HN not only had minimal NA activity but also was unable to absorb chicken erythrocytes, even though it was transported to the cell surface in normal amounts, in an apparently antigenic form. Attachment function was restored to the protein by the introduction of the additional substitution(s) at 129 and/or 193. These results indicate that residue 175 influences not only NA activity but also receptor recognition.