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

Proceedings of the National Academy of Sciences of the United States of America
Oliver LenzWolfgang Garten

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.

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Citations

Mar 14, 2007·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Nabil G Seidah, Annik Prat
May 29, 2008·Archives of Virology·Shuiyun LanYuying Liang
Mar 5, 2003·Antiviral Research·Christian DrostenStephan Günther
Jun 12, 2012·Nature Reviews. Drug Discovery·Nabil G Seidah, Annik Prat
Feb 13, 2008·Proceedings of the National Academy of Sciences of the United States of America·Sheli R RadoshitzkyMichael Farzan
Nov 30, 2011·Proceedings of the National Academy of Sciences of the United States of America·Sébastien IgonetFélix A Rey
Aug 3, 2010·The Journal of Biological Chemistry·Ryan K SwenertonJames H McKerrow
Nov 12, 2010·The Journal of Biological Chemistry·Klára BriknarováJack H Nunberg
Dec 6, 2007·The Journal of Infectious Diseases·Ute StröherHeinz Feldmann
Apr 26, 2012·Journal of Virology·Christelle PythoudStefan Kunz
Jul 25, 2009·Journal of Virology·Sudhakar S AgnihothramJack H Nunberg
Jan 21, 2009·Journal of Virology·François-Loic CossetBirke Bartosch
Nov 26, 2010·Journal of Virology·Giulia PasqualStefan Kunz
Jan 15, 2010·Journal of Virology·Katrin SchlieWolfgang Garten
Jan 29, 2010·Journal of Virology·Allison GrosethStephan Becker
Apr 23, 2002·Journal of Virology·Christina F SpiropoulouMichael B A Oldstone
Jun 20, 2002·Journal of Virology·Angela J SanchezStuart T Nichol
Jul 30, 2003·Journal of Virology·Martin J VincentStuart T Nichol
Sep 29, 2005·Journal of Virology·Kelly Ann MeulendykeRebecca Ellis Dutch
Sep 29, 2005·Journal of Virology·Cara Theresia Pager, Rebecca Ellis Dutch

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