Gene and protein sequence of an influenza neuraminidase with hemagglutinin activity

An influenza virus neuraminidase (NA) of the N9 subtype also has hemagglutinin (HA) activity (W. G. Laver, P. M. Colman, R. G. Webster, V. S. Hinshaw, and G. M. Air (1984), Virology 137, 314-323). To determine sequence relationships between this NA and other known NA and HA subtype sequences, and as a necessary step toward a complete structure determination, we have cloned a full-length copy of the coding sequence of the N9 NA of influenza virus A/tern/Australia/G70C/75 into the plasmid pUC9 using SalI linkers. The gene was sequenced by directed subcloning into the single-stranded phage vectors M13mp19 and M13mp18 and use of the dideoxy procedure. Most of the NA sequence was also obtained by direct protein sequencing of tryptic peptides. The N9 NA has 43 and 44% homology when compared to N1 or N2 sequences, respectively. There is no significant homology to any known HA sequence, or to the HN protein of the paramyxovirus SV5. Like the other NA molecules, the N9 NA is anchored in the membrane by an N-terminal hydrophobic region, from which biologically active heads can be released by pronase.