Molecular Insights into Crimean-Congo Hemorrhagic Fever Virus

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

Overall, CCHFV glycoproteins appear to be involved in entry and fusion, virion formation and immune evasion. Gn and Gc are believed to mediate entry and fusion. Their functions are for the most part extrapolated from those of glycoproteins from distantly related bunyaviruses. The cytoplasmic tail of Gn contains a zinc finger domain that binds RNA in vitro, suggesting that Gn may interact with RNA and perform matrix protein-like functions [53] . However, as RNA [3] is encapsidated in the RNP, it is not clear how Gn might bind and incorporate RNP into the nascent virions. Functional studies of the CCHFV GPC highlighted the essential role of the PreGn convertase SKI-1/S1P in the production of infectious particles [54] . Importantly, PreGn and PreGc normally localize in the Golgi complex, which implies that correct processing of these proteins regulates the production of infectious CCHFV particles [54] . Determining the function of GP38 is particularly intriguing as it is nairovirus-specific and does not share sequence homology with other cellular or viral proteins. Furin cleavage was shown to selectively block GP38 production without affecting the secretion of the cleavage products of SKI-1/S1P: GP160 and GP85 [51, 56] . Blocking furin cleavage resulted in a transient reduction in viral titers, implying that mature GP38 is not important for CCHFV replication, at least in cell culture. In addition, blocking furin cleavage also results in a slight reduction in PreGn processing, showing that furin cleavage might indirectly regulate SKI-1/S1P-dependent GPC processing [56] .