Molecular Insights into Crimean-Congo Hemorrhagic Fever Virus

Zivcec, Marko; Scholte, Florine E. M.; Spiropoulou, Christina F.; Spengler, Jessica R.; Bergeron, Éric

Limited endoproteolysis PreGn and PreGc is required to complete GPC maturation. The host protease required to convert PreGc to Gc remains unidentified. Given that the PreGc cleavage motif of CCHFV (RKPL) is identical to the GPC cleavage motif of Guanarito virus, an arenavirus [60] that is cleaved by the subtilisin kexin isozyme-1/site-1 protease (SKI-1/S1P), this same protease or a protease with similar specificity (SKI/S1P-like) may cleave CCHFV PreGc. The cleavage of PreGn by SKI-1/S1P occurs early in the secretory pathway, either in the ER or after its exit to the cis-Golgi apparatus [58] . PreGn cleavage at the RRLL motif liberates N-terminal products (GP160 and GP85), containing the MLD and GP38 domain [58] . GP160/85 can be further cleaved in the trans-Golgi network (TGN) by furin at a well-conserved RSKR motif located at the junction of the MLD and the GP38 domain [51] . This cleavage is predicted to free the GP38 domain from the MLD, although available antibodies can only detect GP38 and the uncleaved MLD-containing glycoproteins (GP160/85), but not the cleaved MLD.