Identification of a Novel C-Terminal Cleavage of Crimean-Congo Hemorrhagic Fever Virus PreG _N That Leads to Generation of an NS _M Protein

Abstract

The structural glycoproteins of Crimean-Congo hemorrhagic fever virus (CCHFV; genus Nairovirus, family Bunyaviridae) are derived through endoproteolytic cleavage of a 1,684-amino-acid M RNA segment-encoded polyprotein. This polyprotein is cotranslationally cleaved into the PreG N and PreG C precursors, which are then cleaved by SKI-1 and a SKI-1-like protease to generate the N termini of G N and G C , respectively. However, the resulting polypeptide defined by the N termini of G N and G C is predicted to be larger (

Crimean-Congo hemorrhagic fever: History, epidemiology, pathogenesis, clinical syndrome and genetic diversity

“…The polyprotein is first cleaved by a host signal peptidase into 140 kDa PreG N and 85 kDa PreG C segments. PreG N is then further cleaved at a number of conserved recognition sites by the host proteases SKI-1 and furin, generating the 58 kDa G N and liberating several small protein fragments, including a nonstructural NSm protein, similar to that which has been identified in other bunyaviruses (Sanchez et al, 2006;Altamura et al, 2007). In cells that lack SKI-1, PreG N and PreG C accumulate in the Golgi apparatus, and infected cells secrete virus particles lacking surface glycoproteins (Bergeron et al, 2007).…”

“…5 and 6) (Altamura et al, 2007;Bertolotti-Ciarlet et al, 2005). The polyprotein is first cleaved by a host signal peptidase into 140 kDa PreG N and 85 kDa PreG C segments.…”

Crimean-Congo Hemorrhagic Fever Virus Glycoprotein Processing by the Endoprotease SKI-1/S1P Is Critical for Virus Infectivity

“…(B) Confluent 175-cm 2 flasks of SRD12B cells or SRD12B cells stably expressing SKI-1 were infected with CCHFV with an MOI of 5. Uninfected (Ϫ) and infected (ϩ) cell supernatants were changed 24 h after the infection and collected at 48 hpi and viral particles purified as essentially as described previously (1). Purified viral pellets were solubilized in 100 l of 2ϫ NuPAGE sample buffer and gamma irradiated with 2 ϫ 10 6 rads prior to electrophoresis.…”

Genomic Characterization of Yogue, Kasokero, Issyk-Kul, Keterah, Gossas, and Thiafora Viruses: Nairoviruses Naturally Infecting Bats, Shrews, and Ticks

“…[11][12][13] The nairovirus M segment encodes a multiplemembrane-spanning polyglycoprotein that is processed by host peptidases to generate the mature envelope glycoproteins (Gn and Gc), a mucin-like protein, and other potential products. [14][15][16][17] The S segment encodes the viral nucleoprotein (N), subunits of which are organized in a head-to-tail manner to encapsidate the viral genome. 18 In CCHFV, the N protein has also been shown to have DNA endonuclease activity 19 and a conserved sequence motif that is characteristic of catalytic motif II of N6-adenine-specific DNA methylases.…”