title: The Lassa virus glycoprotein precursor GP-C is proteolytically processed by subtilase SKI-1/S1P.
abstract: The surface glycoprotein of the Lassa virus, a member of the arenaviridae family, is synthesized as a 76-kDa precursor (GP-C) that is posttranslationally cleaved into an N-terminal 44-kDa subunit and a C-terminal membrane-anchored 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 endoplasmic 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 virions 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 glycoprotein processing, one that may be an interesting target for antiviral therapy.
authors.affiliation: Institute of Virology, Philipps University, Robert-Koch-Strasse 17, 35037 Marburg, Germany.
authors.forename: O
authors.initials: O
authors.lastname: Lenz
authors.forename: J
authors.initials: J
authors.lastname: ter Meulen
authors.forename: H D
authors.initials: HD
authors.lastname: Klenk
authors.forename: N G
authors.initials: NG
authors.lastname: Seidah
authors.forename: W
authors.initials: W
authors.lastname: Garten
mesh_terms: D000818:Animals; D016466:CHO Cells; D000001:Calcimycin / Q000494:pharmacology; D002642:Chick Embryo; D002522:Chlorocebus aethiops; D006224:Cricetinae; D007836:Lassa virus / Q000187:drug effects / Q000378:metabolism; D043484:Proprotein Convertases; D011498:Protein Precursors / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000502:physiology*; D014162:Transfection; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000378:metabolism*
chemical_list: D011498:Protein Precursors; D014759:Viral Envelope Proteins; C066508:glycoprotein gp1, lassa virus; C077198:glycoprotein gp2, lassa virus; D000001:Calcimycin; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; C115575:membrane-bound transcription factor peptidase, site 1