Molecular Insights into Crimean-Congo Hemorrhagic Fever Virus

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

Following cell entry and fusion, the genomic RNPs are released into the cytosol and the encapsidated vRNA serves as a template for the L protein to synthesize viral mRNA ( Figure 1 ). No studies have described the 3 1 termini of nairovirus mRNA or elements involved in terminating transcription. However, the 5 1 terminal regions of Dugbe virus, a related nairovirus, contain a 7-methylguanylate (m7G) cap with sequences derived from cellular mRNA. To initiate viral mRNA synthesis, the L protein uses m7G capped primers that are snatched from cellular mRNA by an endonuclease domain located in the L protein. CCHFV L protein contains a residue (D693) [25] that is predicted to coordinate a Mn 2+ critical for the cap snatching activity, as demonstrated for endonucleases of other L proteins [48] [49] [50] . Mutating D693 selectively abolishes L protein transcription activity, but does not impair its ability to replicate CCHFV genome analogues [26] . This suggests that capped primers are not used to initiate CCHFV replication.