The Lassa virus glycoprotein precursor GP-C is proteolytically processed by subtilase SKI-1/S1P

The surface glycoprotein of the Lassa virus, a member of the arenaviridae f amily, is synthesized as a 76-kDa precursor (GIP-C) that is posttranslation ally cleaved into an N-terminal 44-kDa subunit and a C-terminal membrane-an chored 36-kDa subunit. Cleavage occurs at the C-terminal end of the unusual recognition motif R-R-L-L. We show here that GP-C is cleaved in the endopl asmic reticulum by the cellular subtilase SKI-1/S1P, an enzyme that has so far been observed to be involved in cholesterol metabolism. Furthermore, we present evidence that only cleaved glycoprotein is incorporated into virio ns and that this is necessary for the formation of infectious virus. To our knowledge, there have been no previous reports of this type of viral glyco protein processing, one that may be an interesting target for antiviral the rapy.