The role of subtilisin-like proprotein convertases for cleavage of the measles virus fusion glycoprotein in different cell types.
The fusion (F) glycoprotein gene of measles virus (MV) encodes a nonfusogenic precursor protein (F0) that is activated by cleavage into the F1 and F2 subunits during transport to the cell surface. The F protein of both the Edmonston strain and a wild-type MV was found to be cleaved in the trans-Golgi cisternae and/or the trans-Golgi network (TGN). In HEp-2 cells, B lymphoblastoid cells, and PBMC, the cleavage process required calcium, and calcium deprivation prevented syncytium formation. The calcium dependence indicated the involvement of the pro-protein convertase (PC) endoprotease family. The expression of the presently recognized members of the PC family in human cell types known to be infected during measles was examined by RT-PCR. Among the PCs residing in the TGN, only furin was expressed in all cells. Soluble secreted human furin produced by a recombinant baculovirus cleaved MV F0 into proteins the exact size of F1 and F2 and increased the titer of MV particles released from calcium-deprived or endoprotease defective infected cells. These results strongly indicate that furin is the most important and maybe the only endoprotease involved in activation of the MV F protein.
Bolt
G
G
Panum Institute, University of Copenhagen, Blegdamsvej 3, Copenhagen N, 2200, Denmark. G.Bolt@immi.ku.dk
Pedersen
I R
IR
D000230:Adenocarcinoma; D002294:Carcinoma, Squamous Cell; D045683:Furin; D006056:Golgi Apparatus / Q000201:enzymology / Q000821:virology; D006801:Humans; D007700:Kinetics; D008459:Measles virus / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D013381:Subtilisins / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014760:Viral Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D010948:Viral Plaque Assay
D011994:Recombinant Proteins; D014760:Viral Fusion Proteins; D012697:Serine Endopeptidases; D013381:Subtilisins; D045683:Furin