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Updated: Jul 21, 2026
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A Fluorogenic Peptide Cleavage Assay to Screen for Proteolytic Activity: Applications for coronavirus spike protein activation
Published on: January 9, 2019
The Lassa virus glycoprotein precursor GP-C is proteolytically processed by subtilase SKI-1/S1P
O Lenz1, J ter Meulen, H D Klenk
1Institute of Virology, Philipps University, Robert-Koch-Strasse 17, 35037 Marburg, Germany.
Summary
Lassa virus glycoprotein precursor (GP-C) is cleaved by SKI-1/S1P in the endoplasmic reticulum. This cleavage is essential for forming infectious Lassa virus, offering a potential antiviral therapy target.
Area of Science:
- Virology
- Molecular Biology
- Biochemistry
Background:
- Lassa virus, an arenaviridae family member, possesses a surface glycoprotein (GP-C).
- GP-C is synthesized as a precursor and posttranslationally cleaved into subunits.
- Cleavage occurs at an unusual R-R-L-L recognition motif.
Purpose of the Study:
- To identify the cellular enzyme responsible for Lassa virus glycoprotein precursor (GP-C) cleavage.
- To investigate the role of GP-C processing in the formation of infectious Lassa virus.
- To explore the potential of this processing pathway as an antiviral target.
Main Methods:
- Investigated the cleavage of Lassa virus GP-C in the endoplasmic reticulum.
- Utilized cellular subtilase SKI-1/S1P for GP-C processing analysis.
- Assessed glycoprotein incorporation into virions and virus infectivity.
Main Results:
- Demonstrated that cellular subtilase SKI-1/S1P cleaves GP-C in the endoplasmic reticulum.
- Showed that only cleaved glycoprotein is incorporated into Lassa virus virions.
- Established that GP-C cleavage is necessary for the formation of infectious virus.
Conclusions:
- Lassa virus glycoprotein processing involves cleavage by SKI-1/S1P, an enzyme previously linked to cholesterol metabolism.
- This novel viral glycoprotein processing pathway is critical for producing infectious Lassa virus.
- The SKI-1/S1P-mediated cleavage represents a potential target for novel antiviral therapies against Lassa virus.
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