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.