Proteolytic processing of human cytomegalovirus glycoprotein B (gpUL55) is mediated by the human endoprotease furin.
Inhibition of endoproteolytic cleavage of glycoprotein B (gB; gpUL55) of human cytomegalovirus was achieved by treatment of infected fibroblasts with decanoyl peptidyl chloromethyl ketone (decRVKR-CMK), which inhibits the action of cellular subtilisin-like endoproteases with the amino acid recognition motif R x K/R R. Uncleaved gB precursor molecules of 160 kDa that were accumulated were endoglycosidase H resistant, suggesting that correct cellular transport occurred in the presence of the drug. The inhibitor also prevented endoproteolytic gB processing in CV-1 cells infected with a recombinant vaccinia virus-gB construct (VVgB). Evidence for direct involvement of the ubiquitous subtilisin-like endoprotease furin in gB cleavage was obtained from the observation that coinfection of CV-1 cells with WgB and a recombinant vaccinia-human furin construct reestablished endoproteolytic activity which was normally absent late after infection with WgB alone.
Vey
M
M
Institut für Virologie, Philipps-Universität, Marburg, Germany.
Schäfer
W
W
Reis
B
B
Ohuchi
R
R
Britt
W
W
Garten
W
W
Klenk
H D
HD
Radsak
K
K
D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000378:metabolism*; D005347:Fibroblasts / Q000821:virology; D045683:Furin; D006801:Humans; D006868:Hydrolysis; D011499:Protein Processing, Post-Translational; D013381:Subtilisins / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000378:metabolism*
D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus; D013381:Subtilisins; D045683:Furin