Molecular Insights into Crimean-Congo Hemorrhagic Fever Virus

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

Until recently, all three segments of CCHFV were believed to each encode a single protein. However, a second protein, the non-structural S (NSS), is encoded in the S segment in the opposite orientation relative to the nucleoprotein (NP) gene, indicating that CCHFV might be considered an ambisense virus ( Figure 2 ) [28] . However, the ambisense coding in CCHFV involves overlapping coding regions. This differs from ambisense coding in bunyaviruses and arenaviruses where the viral proteins are encoded in opposite orientation, and separated by an intergenic region that serves as a transcription termination signal [29, 30] . In contrast to the S segment (~1.6 kb), that is comparable in size to other bunyaviruses, the M (~5.4 kb) and L (~12.1 kb) segments of CCHFV are significantly larger than those of other bunyaviruses, and contain a single gene encoding the glycoprotein precursor (GPC) and the L protein, respectively. The genome segments or viral RNA (vRNA) are encapsidated with NP and L protein to form genomic ribonucleoprotein complexes (RNP). The genomic RNPs are packaged into viral particles by acquiring a lipid envelope and the surface glycoproteins Gn and Gc [31] (Figure 1 ). Electron microscopy studies of nairoviruses report spherical particles of relatively uniform size with a diameter of ~90-100 nm with small (<10 nm) spike-like projections from the surface of the Figure 2 . CCHFV genome. CCHFV possess a tri-segmented negative sense RNA genome. The small (~1.6 kb), medium (~5.4 kb) and large (~12.1 kb) segments, code for the NP, the GPC and the L protein, respectively. The small segment also codes for a non-structural S protein (NS S ) in the positive sense. The coding regions are flanked by non-coding regions (NCRs). The nucleotide lengths of the regions (both coding and non-coding) are displayed and based on full-length sequences available in GenBank.