Identification of a Novel C-Terminal Cleavage of Crimean-Congo Hemorrhagic Fever Virus PreG N That Leads to Generation of an NS M Protein
- 15 June 2007
- journal article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 81 (12), 6632-6642
- https://doi.org/10.1128/jvi.02730-06
Abstract
The structural glycoproteins of Crimean-Congo hemorrhagic fever virus (CCHFV; genus Nairovirus , family Bunyaviridae ) are derived through endoproteolytic cleavage of a 1,684-amino-acid M RNA segment-encoded polyprotein. This polyprotein is cotranslationally cleaved into the PreG N and PreG C precursors, which are then cleaved by SKI-1 and a SKI-1-like protease to generate the N termini of G N and G C , respectively. However, the resulting polypeptide defined by the N termini of G N and G C is predicted to be larger (58 kDa) than mature G N (37 kDa). By analogy to the topologically similar M segment-encoded polyproteins of viruses in the Orthobunyavirus genus, the C-terminal region of PreG N that contains four predicted transmembrane domains may also contain a nonstructural protein, NS M . To characterize potential PreG N C-terminal cleavage events, a panel of epitope-tagged PreG N truncation and internal deletion mutants was developed. These constructs allowed for the identification of a C-terminal endoproteolytic cleavage within, or very proximal to, the second predicted transmembrane domain following the G N ectodomain and the subsequent generation of a C-terminal fragment. Pulse-chase experiments showed that PreG N C-terminal cleavage occurred shortly after synthesis of the precursor and prior to generation of the G N glycoprotein. The resulting fragment trafficked to the Golgi compartment, the site of virus assembly. Development of an antiserum specific to the second cytoplasmic loop of PreG N allowed detection of cell-associated NS M proteins derived from transient expression of the complete CCHFV M segment and also in the context of virus infection.Keywords
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