The "Spanish" influenza pandemic of 1918 was characterized by exceptionally
high mortality, especially among young adults. The surface proteins of inf
luenza viruses, hemagglutinin and neuraminidase, play important roles in vi
rulence, host specificity, and the human immune response. The complete codi
ng sequence of hemagglutinin was reported last year. This laboratory has no
w determined the complete coding sequence of the neuraminidase gene of the
1918 virus. Influenza RNA fragments were isolated from lung tissue of three
victims of the 1918 flu; complete sequence was generated from A/Brevig Mis
sion/1/18, with confirmatory sequencing carried out on A/South Carolina/1/1
8 and A/New York/1/18. The 1918 neuraminidase gene sequence was compared wi
th other N1 subtype neuraminidase genes, including 9 N1 strains newly seque
nced for this study. The 1918 neuraminidase shares many sequence and struct
ural characteristics with avian strains, including the conserved active sit
e, wild-type stalk length, glycosylation sites, and antigenic sites. Phylog
enetically, the 1918 neuraminidase gene appears to be intermediate between
mammals and birds, suggesting that it was introduced into mammals just befo
re the 1918 pandemic.