Crimean–Congo hemorrhagic fever virus genome L RNA segment and encoded protein

Abstract

Sequence analysis of the L RNA genome segment and predicted encoded L polymerase protein of Crimean-Congo hemorrhagic fever (CCHF) virus (genus Nairovirus, family Bunyaviridae) demonstrates that they are approximately twice the size of those found in viruses of other bunyavirus genera. The CCHF virus L segment and encoded protein (12,164 nucleotides and 3944 amino acids, respectively) are similar in size and sequence to those of the nairovirus Dugbe virus (12,255/62% and 4036/62% nucleotide and amino acid length/identity, respectively). The identification of an ovarian tumor (OTU)-like protease motif in the L protein amino termini of the nairoviruses Dugbe, CCHF, and Nairobi sheep disease (NSD) indicates these proteins are members of the recently described OTU-like protease family and suggests that these large proteins may be polyproteins that are autoproteolytically cleaved or involved in deubiquitination.

Kupe Virus, a New Virus in the FamilyBunyaviridae, GenusNairovirus, Kenya

“…The Kupe virus ORF aa sequence shows a high degree of homology to that of DUGV, with the exception of a highly variable region (Kupe virus aa 755-896) that shows low homology (24.8%) and in which the DUGV sequence is 14 aa shorter than Kupe virus (42 nt deletion in DUGV relative to Kupe virus). In this same region, a 92-nt deletion has been shown in CCHFV relative to DUGV, and a similar deletion is observed in HAZV (17). All conserved motifs in the RNA-dependent RNA polymerase (RDRP) module (region 3), as well as other conserved domains upstream and downstream of the polymerase module (regions 1, 2, and 4), were conserved in the Kupe virus ORF, as shown in DUGV and CCHFV (16).…”

“…All conserved motifs in the RNA-dependent RNA polymerase (RDRP) module (region 3), as well as other conserved domains upstream and downstream of the polymerase module (regions 1, 2, and 4), were conserved in the Kupe virus ORF, as shown in DUGV and CCHFV (16). Kupe virus L segment ORF also contains several protein motifs previously identifi ed in DUGV and CCHFV, including an ovarian tumor-like cysteine protease domain, a DNA topoisomerase-like domain (aa 76-94), and a C2H2-type zinc fi nger motif (aa 608-631) (17,18). However, Kupe virus ORF did not contain the leucine zipper motif identifi ed in CCHFV and DUGV.…”

Crimean–Congo hemorrhagic fever

“…Furthermore, high-sequence homology with a newly formed superfamily of predicted cysteine proteases, termed ovarian tumor (OTU)-like proteases, was discovered, which was also suggested from the L segment sequence of Dugbe virus (Makarova et al, 2000). From these data, it is hypothesized that the OTU-like protease may function in the Nairovirus L protein by autoproteolytically cleaving the polyprotein to yield a polymerase and a helicase (Honig et al, 2004;Kinsella et al, 2004). Other suggested functions of the OTU-like protease include involvement with deubiquitination activitites, such that has recently been demonstrated for the adenovirus L3 23 K proteinase (Balakirev et al, 2002).…”

“…Virions of members of the family Bunyaviridae contain three structural proteins: two envelope glycoproteins (G2 and G1 [more recently termed Gn and Gc, respectively, named in accordance with their relative proximity to the amino or carboxy terminus of the M segment encoded polyprotein]) and a nucleocapsid protein (N), plus a large polypeptide (L) (approximately 200 kDa), which is the viron-associated RNA-dependent RNA polymerase (Schmaljohn and Hooper, 2001;Marriott and Nuttall, 1996b). Recently, two independent research groups published the complete nucleotide sequence of the CCHFV L segment (Honig et al, 2004;Kinsella et al, 2004). The sequence is approximately 60% identical both at the nucleotide and amino acid levels to the L segment of Dugbe virus, the only other Nairovirus genome to be fully sequenced, with the most highly conserved area being that encoding the region corresponding to the core catalytic domains of the RNA-dependent RNA polymerase.…”

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

“…Its single open reading frame, more than 12,000 nucleotides in length, encodes a nearly 4000-amino acid polyprotein, which contains an ovarian tumor protease (OTU) domain near its N-terminus, followed by segments homologous to viral topoisomerase, zinc finger and leucine zipper motifs, and a RdRp catalytic domain near the C-terminus (Honig et al, 2004a). The latter show extensive sequence identity with Dugbe virus, another member of the Nairovirus genus.…”