251. Crimean-Congo hemorrhagic fever virus glycoprotein processing by the endoprotease SKI-1/S1P is critical for virus infectivity.
- Author
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Bergeron E, Vincent MJ, and Nichol ST
- Subjects
- Animals, CHO Cells, Cricetinae, Cricetulus, Genetic Complementation Test, Golgi Apparatus chemistry, Humans, Proprotein Convertases deficiency, Protein Processing, Post-Translational physiology, Serine Endopeptidases deficiency, Virion chemistry, Glycoproteins metabolism, Hemorrhagic Fever Virus, Crimean-Congo physiology, Proprotein Convertases metabolism, Serine Endopeptidases metabolism, Viral Structural Proteins metabolism
- Abstract
Crimean-Congo hemorrhagic fever virus (CCHFV) causes severe human disease. The CCHFV medium RNA encodes a polyprotein which is proteolytically processed to yield the glycoprotein precursors PreGn and PreGc, followed by structural glycoproteins Gn and Gc. Subtilisin kexin isozyme-1/site-1 protease (SKI-1/S1P) plays a central role in Gn processing. Here we show that CCHFV-infected cells deficient in SKI-1/S1P produce no infectious virus, although PreGn and PreGc accumulated normally in the Golgi apparatus, the site of virus assembly. Only nucleoprotein-containing particles which lacked virus glycoproteins (Gn/Gc or PreGn/PreGc) were secreted. Complementation of SKI-1/S1P-deficient cells with a SKI-1/S1P expression vector restored release of infectious virus (>10(6) PFU/ml), confirming that SKI-1/S1P processing is required for incorporation of viral glycoproteins. SKI-1/S1P may represent a promising antiviral target.
- Published
- 2007
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