Envelope glycoprotein of arenaviruses.

Abstract

Arenaviruses include lethal human pathogens which pose serious public health threats. So far, no FDA approved vaccines are available against arenavirus infections, and therapeutic options are limited, making the identification of novel drug targets for the development of efficacious therapeutics an urgent need. Arenaviruses are comprised of two RNA genome segments and four proteins, the polymerase L, the envelope glycoprotein GP, the matrix protein Z, and the nucleoprotein NP. A crucial step in the arenavirus life-cycle is the biosynthesis and maturation of the GP precursor (GPC) by cellular signal peptidases and the cellular enzyme Subtilisin Kexin Isozyme-1 (SKI-1)/Site-1 Protease (S1P) yielding a tripartite mature GP complex formed by GP1/GP2 and a stable signal peptide (SSP). GPC cleavage by SKI-1/S1P is crucial for fusion competence and incorporation of mature GP into nascent budding virion particles. In a first part of our review, we cover basic aspects and newer developments in the biosynthesis of arenavirus GP and its molecular interaction with SKI-1/S1P. A second part will then highlight the potential of SKI-1/S1P-mediated processing of arenavirus GPC as a novel target for therapeutic intervention to combat human pathogenic arenaviruses.

• Authors: Dominique J Burri, Joel Ramos da Palma, Stefan Kunz, Antonella Pasquato
• Journal: Viruses (Viruses) Vol. 4 Issue 10 Pg. 2162-81 (Oct 17 2012) ISSN: 1999-4915 [Electronic] Switzerland
• PMID: 23202458 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antiviral Agents
• PF-429242
• Protein Sorting Signals
• Pyrrolidines
• Receptors, Cell Surface
• Viral Envelope Proteins
• Proprotein Convertases
• Serine Endopeptidases
• membrane-bound transcription factor peptidase, site 1

Topics

• Amino Acid Sequence
• Antiviral Agents (pharmacology)
• Arenaviridae Infections (drug therapy, metabolism, virology)
• Arenavirus (drug effects, metabolism, pathogenicity)
• Glycosylation
• Golgi Apparatus (metabolism, virology)
• Humans
• Proprotein Convertases (antagonists & inhibitors, metabolism)
• Protein Sorting Signals
• Proteolysis
• Pyrrolidines (pharmacology)
• Receptors, Cell Surface (metabolism)
• Serine Endopeptidases (metabolism)
• Viral Envelope Proteins (biosynthesis, chemistry)
• Virus Assembly
• Virus Attachment