TY - JOUR
T1 - Rescue of the highly virulent classical swine fever virus strain “Koslov” from cloned cDNA and first insights into genome variations relevant for virulence
AU - Fahnøe, Ulrik
AU - Pedersen, Anders Gorm
AU - Risager, Peter Christian
AU - Nielsen, Jens
AU - Belsham, Graham
AU - Höper, Dirk
AU - Beer, Martin
AU - Rasmussen, Thomas Bruun
PY - 2014
Y1 - 2014
N2 - Classical swine fever virus (CSFV) strain “Koslov” is highly virulent with a mortality rate of up to 100% in pigs. In this study, we modified non-functional cDNAs generated from the blood of Koslov virus infected pigs bysite-directed mutagenesis, removing non-synonymous mutations step-by-step, thereby producing genomes encoding the consensus amino acid sequence. Viruses rescued from the construct corresponding to the inferred parental form were highly virulent, when tested in pigs, with infected animals displaying pronounced clinical symptoms leading to high mortality. The reconstruction therefore gave rise to a functional cDNA corresponding to the highly virulent Koslov strain of CSFV. It could be demonstrated that two single amino acid changes (S763L and P968H) in the surface structural protein E2 resulted in attenuation in the porcine infection system while another single amino acid change within the nonstructural protein NS3 (D2183G) reduced virus growth within cells in vitro.
AB - Classical swine fever virus (CSFV) strain “Koslov” is highly virulent with a mortality rate of up to 100% in pigs. In this study, we modified non-functional cDNAs generated from the blood of Koslov virus infected pigs bysite-directed mutagenesis, removing non-synonymous mutations step-by-step, thereby producing genomes encoding the consensus amino acid sequence. Viruses rescued from the construct corresponding to the inferred parental form were highly virulent, when tested in pigs, with infected animals displaying pronounced clinical symptoms leading to high mortality. The reconstruction therefore gave rise to a functional cDNA corresponding to the highly virulent Koslov strain of CSFV. It could be demonstrated that two single amino acid changes (S763L and P968H) in the surface structural protein E2 resulted in attenuation in the porcine infection system while another single amino acid change within the nonstructural protein NS3 (D2183G) reduced virus growth within cells in vitro.
U2 - 10.1016/j.virol.2014.08.021
DO - 10.1016/j.virol.2014.08.021
M3 - Journal article
C2 - 25240324
SN - 0042-6822
VL - 468-470
SP - 379
EP - 387
JO - Virology
JF - Virology
ER -