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 fibrobl asts with decanoyl peptidyl chloromethyl ketone (decRVKR-CMK), which i nhibits the action of cellular subtilisin-like endoproteases with the amino acid recognition motif R X K/R R. Uncleaved gB precusor molecule s of 160 kDa that were accumulated were endoglycosidase H resistant, s uggesting that correct cellular transport occurred in the presence of the drug. The inhibitor also prevented endoproteolytic gB processing i n CV-1 cells infected with a recombinant vaccinia virus-gB construct ( WgB). Evidence for direct involvement of the ubiquitous subtilisin-lik e endoprotease furin in gB cleavage was obtained from the observation that coinfection of CV-1 cells with WgB and a recombinant vaccinia-hum an furin construct reestablished endoproteolytic activity which was no rmally absent late after infection with WgB alone. (C) 1995 Academic P ress, Inc.