The Sendai virus envelope contains two glycoproteins: the fusion (F) protein and the hemaggiutinin-neuraminidase (HN). Inactivation of F causes the loss of fusogenic activity and an increase of the neuraminidase activity of HN. After inactivation of F, HN can be inhibited by fetuin or asialofetuin, as already observed on the water-soluble, C-terminal fragment of HN (Dallocchio, F., Bellini, T., Martuscelli, G., Baiocchi, M., and Tomasi, M. (1991) Biochem. Int. 25, 663-668). Disruption of viral envelopes by detergents does not affect the neuraminidase activity of virions contaning inactive F, while it causes an increase of the neuraminidase activity in native virions. Reconstitution of HN into liposomes is accompanied by a decrease of enzymatic activity, due to the random inside-outside distribution of the protein. However, the decrease of the neuraminidase activity is higher in liposomes contianig both HN and F. These data suggest that F inhibits the neuraminidase activity of HN. (C) 1994 Academic Press, Inc.