Cytopathogenicity markers in the genome of Hungarian cytopathic isolates of bovine viral diarrhoea virus

Abstract

Since genetic recombination is a major factor in the evolution of the cytopathogenic (cp) bovine viral diarrhoea virus (BVDV) biotypes, in this study the cytopathogenicity markers were investigated in the genomes of two cp BVDV strains recently isolated from mucosal disease (MD) cases in Hungary. In the genome of strain H4956, a Jiv-like insertion was found similar to those described in reference strain NADL and in other BVDV 1, BVDV 2 and border disease virus (BDV) strains. The 133 amino acid Jiv-like sequence is inserted at nucleotide position 4984 (amino acid position 1533), 9 nucleotides upstream of that of strain NADL. The insertion showed 96% amino acid sequence identity with the cellular Jiv protein. In the genome of cp BVDV strain H115/PCR, an ubiquitin-containing duplication was found. The duplicated sequence started at nucleotide position 7978 (amino acid 2531) in the NS4B gene. The duplication contained a complete ubiquitin monomer of 76 amino acids and the complete NS3 gene starting at nucleotide position 5153 (amino acid 1589), which corresponds to the first Nterminal amino acid of NS3. The duplication was located further downstream of the known ubiquitin-containing genomic regions of cp BVDV strains, and it consisted of the shortest inserted nucleotide sequence. The insertions and duplication of strains H4956 and H115/PCR further confirmed that recombinations occurring at positions A and B are the most common mechanisms leading to the development of BVDV cytopathogenicity.

Complete Genome Sequences of a Cytopathic/Noncytopathic Pair of Border Disease Viruses

“…CB5c had a 288-base insertion derived from the Jiv cellular transcript (8, 9) in the NS2/NS3 coding region. Similar inserts were observed in BVDV type 2 cp genomes (1, 10). Excluding the insert, the two viruses had 37 nucleotide differences and 11 amino acid changes.…”

“…Like bovine viral diarrhea virus (BVDV), BDV can be classified as noncytopathic (ncp) or cytopathic (cp) based on its growth characteristics in vitro . For BVDV, the cp form arises from the ncp virus by insertions of cellular sequences or rearrangement and duplication of viral sequences (1–5). When infection of a pregnant animal occurs in the first trimester of pregnancy with an ncp virus, the fetus can become persistently infected (PI).…”

The Molecular Biology of Pestiviruses

“…Over time, a large number of additional cp pestivirus strains with insertions derived from the Jiv/DNAJ-C14 gene were identified, including BVDV-1 and -2, border disease virus, Hobi-like pestivirus, and an isolate from giraffe (Avalos-Ramirez, Orlich, Balint, Baule, Kecskemeti, Kiss, & Belak, 2005;Becher, Meyers, Shannon, & Thiel, 1996;Darweesh et al, 2015;Decaro et al, 2012;Meyers et al, 1990;M€ uller, Rinck, Thiel, & Tautz, 2003;Nagai et al, 2003;Ridpath & Neill, 2000;Rinck et al, 2001;Vilcek, GreiserWilke, Nettleton, & Paton, 2000). Most of these insertions were located in the C-terminal part of NS2 between amino acids 1528 and 1544.…”

Dengue virus NS4B interacts with NS3 and dissociates it from single-stranded RNA

“…Deletion of NS4B, as well as insertions in its sequence, inhibit replication of both Bovine viral diarrhea virus (BVDV) and Kunjin viruses (Balint et al, 2005;Grassmann et al, 2001;Khromykh et al, 2000;Li & McNally, 2001). BVDV NS4B interacts with NS3 and NS5A (Qu et al, 2001) and HCV NS4B plays a role in viral RNA replication, possibly by inducing morphological changes in the ER membrane (Egger et al, 2002;Gretton et al, 2005;Piccininni et al, 2002).…”