Influenza virus hemagglutinin with multibasic cleavage site is activated by furin, a subtilisin-like endoprotease.
Many viruses have membrane glycoproteins that are activated at cleavage sites containing multiple arginine and lysine residues by cellular proteases so far not identified. The proteases responsible for cleavage of the hemagglutinin of fowl plague virus, a prototype of these glycoproteins, has now been isolated from Madin-Darby bovine kidney cells. The enzyme has a mol. wt of 85,000, a pH optimum ranging from 6.5 to 7.5, is calcium dependent and recognizes the consensus sequence R-X-K/R-R at the cleavage site of the hemagglutinin. Using a specific antiserum it has been identified as furin, a subtilisin-like eukaryotic protease. The fowl plague virus hemagglutinin was also cleaved after coexpression with human furin from cDNA by vaccinia virus vectors. Peptidyl chloroalkylketones containing the R-X-K/R-R motif specifically bind to the catalytic site of furin and are therefore potent inhibitors of hemagglutinin cleavage and fusion activity.
Stieneke-Gröber
A
A
Institut für Virologie, Philipps-Universität Marburg, Germany.
Vey
M
M
Angliker
H
H
Shaw
E
E
Thomas
G
G
Roberts
C
C
Klenk
H D
HD
Garten
W
W
D000345:Affinity Labels; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002417:Cattle; D002478:Cells, Cultured; D002642:Chick Embryo; D002853:Chromatography, Liquid; D004247:DNA; D004285:Dogs; D045683:Furin; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009980:Influenza A virus / Q000201:enzymology* / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D013381:Subtilisins / Q000378:metabolism*; D014616:Vaccinia virus / Q000235:genetics; D014759:Viral Envelope Proteins / Q000378:metabolism*
D000345:Affinity Labels; D000590:Amino Acid Chloromethyl Ketones; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D008565:Membrane Proteins; D014759:Viral Envelope Proteins; D004247:DNA; D013381:Subtilisins; D045683:Furin