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PMID: 11606739 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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 ·Vol. 98 ·No. 22 ·2001-10-23 ·Pages 12701-5

Lenz O, ter Meulen J, Klenk HD, Seidah NG, Garten W

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.

MeSH Terms
Animals CHO Cells Calcimycin/pharmacology Chick Embryo Chlorocebus aethiops Cricetinae Lassa virus/drug effects,metabolism Proprotein Convertases Protein Precursors/metabolism Serine Endopeptidases/physiology Transfection Vero Cells Viral Envelope Proteins/metabolism
Chemicals
Protein Precursors Viral Envelope Proteins glycoprotein gp1, lassa virus glycoprotein gp2, lassa virus Calcimycin Proprotein Convertases Serine Endopeptidases membrane-bound transcription factor peptidase, site 1
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Lenz O
Institute of Virology, Philipps University, Robert-Koch-Strasse 17, 35037 Marburg, Germany.
ter Meulen J
Klenk H D
Seidah N G
Garten W
References (28)
28 references, click to expand
  1. Processing of viral glycoproteins by the subtilisin-like endoprotease furin and its inhibition by specific peptidylchloroalkylketones.
    Biochimie. 1994;76(3-4):217-25 PMID: 7819326
  2. Host cell proteases controlling virus pathogenicity.
    Trends Microbiol. 1994 Feb;2(2):39-43 PMID: 8162439
  3. Cleavage of sterol regulatory element-binding proteins (SREBPs) at site-1 requires interaction with SREBP cleavage-activating protein. Evidence from in vivo competition studies.
    J Biol Chem. 1998 Mar 6;273(10):5785-93 PMID: 9488713
  4. The matrix protein of HIV-1 is not sufficient for assembly and release of virus-like particles.
    Virology. 1998 Aug 15;248(1):108-16 PMID: 9705260
  5. Isolation of cholesterol-requiring mutant Chinese hamster ovary cells with defects in cleavage of sterol regulatory element-binding proteins at site 1.
    J Biol Chem. 1998 Oct 23;273(43):28261-9 PMID: 9774448
  6. Molecular identification of the sterol-regulated luminal protease that cleaves SREBPs and controls lipid composition of animal cells.
    Mol Cell. 1998 Oct;2(4):505-14 PMID: 9809072
  7. Identification of alpha-dystroglycan as a receptor for lymphocytic choriomeningitis virus and Lassa fever virus.
    Science. 1998 Dec 11;282(5396):2079-81 PMID: 9851928
  8. Mammalian subtilisin/kexin isozyme SKI-1: A widely expressed proprotein convertase with a unique cleavage specificity and cellular localization.
    Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1321-6 PMID: 9990022
  9. Autocatalytic processing of site-1 protease removes propeptide and permits cleavage of sterol regulatory element-binding proteins.
    J Biol Chem. 1999 Aug 6;274(32):22795-804 PMID: 10428864
  10. Transport-dependent proteolysis of SREBP: relocation of site-1 protease from Golgi to ER obviates the need for SREBP transport to Golgi.
    Cell. 1999 Dec 23;99(7):703-12 PMID: 10619424
  11. Biosynthesis and enzymatic characterization of human SKI-1/S1P and the processing of its inhibitory prosegment.
    J Biol Chem. 2000 Jan 28;275(4):2349-58 PMID: 10644685
  12. The subtilisin/kexin family of precursor convertases. Emphasis on PC1, PC2/7B2, POMC and the novel enzyme SKI-1.
    Ann N Y Acad Sci. 1999 Oct 20;885:57-74 PMID: 10816641
  13. Identification of a novel consensus sequence at the cleavage site of the Lassa virus glycoprotein.
    J Virol. 2000 Dec;74(23):11418-21 PMID: 11070044
  14. ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs.
    Mol Cell. 2000 Dec;6(6):1355-64 PMID: 11163209
  15. Short communication: Lassa fever in Sierra Leone: UN peacekeepers are at risk.
    Trop Med Int Health. 2001 Jan;6(1):83-4 PMID: 11251899
  16. The viral transmembrane superfamily: possible divergence of Arenavirus and Filovirus glycoproteins from a common RNA virus ancestor.
    BMC Microbiol. 2001;1:1 PMID: 11208257
  17. Pathologic and virologic study of fatal Lassa fever in man.
    Am J Pathol. 1982 Jun;107(3):349-56 PMID: 7081389
  18. Inhibition of proteolytic cleavage of the hemagglutinin of influenza virus by the calcium-specific ionophore A23187.
    EMBO J. 1984 Dec 1;3(12):2911-5 PMID: 6441705
  19. Electroblotting of multiple gels: a simple apparatus without buffer tank for rapid transfer of proteins from polyacrylamide to nitrocellulose.
    J Biochem Biophys Methods. 1984 Dec;10(3-4):203-9 PMID: 6530509
  20. Lassa fever. Effective therapy with ribavirin.
    N Engl J Med. 1986 Jan 2;314(1):20-6 PMID: 3940312
  21. A prospective study of the epidemiology and ecology of Lassa fever.
    J Infect Dis. 1987 Mar;155(3):437-44 PMID: 3805771
  22. A case-control study of the clinical diagnosis and course of Lassa fever.
    J Infect Dis. 1987 Mar;155(3):445-55 PMID: 3805772
  23. Rapid redistribution of Golgi proteins into the ER in cells treated with brefeldin A: evidence for membrane cycling from Golgi to ER.
    Cell. 1989 Mar 10;56(5):801-13 PMID: 2647301
  24. Structure and assembly of hemagglutinin mutants of fowl plague virus with impaired surface transport.
    J Virol. 1992 Mar;66(3):1495-505 PMID: 1738202
  25. The fusion of artificial lipid membranes induced by the synthetic arenavirus 'fusion peptide'.
    Biochim Biophys Acta. 1992 Oct 5;1110(2):202-8 PMID: 1390849
  26. Mechanism of lymphocytic choriomeningitis virus entry into cells.
    Virology. 1994 Jan;198(1):1-9 PMID: 8259643
  27. Enhanced gene delivery and mechanism studies with a novel series of cationic lipid formulations.
    J Biol Chem. 1994 Jan 28;269(4):2550-61 PMID: 8300583
  28. Non-replicating vaccinia vector efficiently expresses bacteriophage T7 RNA polymerase.
    FEBS Lett. 1995 Aug 28;371(1):9-12 PMID: 7664891
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.221447598
Published
2001-10-23
Epub
2001-00-16
Pages
12701-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC60117
Subset
IM
Grants
PHS HHS · 75301564301 · United States
External Links
PubMed source DOI: 10.1073/pnas.221447598 PMC Full Text View journal details
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