ACTIVATION OF AN INFLUENZA-VIRUS A TURKEY/OREGON/71 HA INSERTION VARIANT BY THE SUBTILISIN-LIKE ENDOPROTEASE FURIN/

The hemagglutinin (HA) gene of the influenza A turkey/Oregon/71 varian t Tc1 adapted to primary chicken embryo cells contains an insertion of 54 nucleotides that encodes a peptide adjacent to the HA cleavage sit e, which is responsible for increased cleavability by ubiquitous cellu lar proteases. After coexpression with human furin from cDNA by vaccin ia virus vectors and by an endogenous protease, the HA of Tc1, which p ossesses the amino acid sequence R-T-A-R at the cleavage site, is prot eolytically processed. Site-directed mutagenesis of the cleavage site indicated that the arginine in position -4 is critical for HA activati on by furin. Deletion of the insert revealed that the amino acid seque nce -1 to -4 predisposes the protein for furin recognition. (C) 1994 A cademic Press, Inc.