Molecular Insights into Crimean-Congo Hemorrhagic Fever Virus

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

The MLD is found in PreGn, GP85, and GP160. Interestingly, the glycoprotein precursors of filoviruses (e.g., Ebola virus and Marburg virus) also contain a MLD and a furin cleavage site [82, 83] . In filoviruses, furin cleavage products, GP1 and GP2, are structural components of virions, and the O-linked glycans of the GP1 MLD can shield and protect GP2 epitopes targeted by neutralizing antibodies [84] . The Ebola virus MLD can be replaced with the CCHFV MLD without affecting protein function, suggesting that the MLD of CCHFV may also shield exposed epitopes [84] . However, the function of the CCHFV MLD may differ significantly from that of filoviruses, as the CCHFV MLD is not incorporated into the viral particles [31] . In addition, truncating the CCHFV MLD is dispensable for the folding and trafficking of GPC [37] . In contrast, longer N-terminal truncation comprising the GP38 domain retains Gn in the ER, suggesting that the GP38 domain has a chaperone activity that assists PreGn folding or frees it from the ER [37] .