Open AccessThe Npro product of classical swine fever virus interacts with IκBα, the NF-κB inhibitor
Author(s) -
Virginie Doceul,
Bryan Charleston,
Helen Crooke,
Elizabeth Reid,
Penny P. Powell,
Julian Seago
Publication year - 2008
Publication title -
journal of general virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.55
H-Index - 167
eISSN - 1465-2099
pISSN - 0022-1317
DOI - 10.1099/vir.0.83643-0
Subject(s) - biology , virology , pestivirus , virus , african swine fever virus , classical swine fever , interferon , innate immune system , apoptosis , transfection , immune system , cell culture , microbiology and biotechnology , flaviviridae , immunology , viral disease , genetics
Classical swine fever virus (CSFV) belongs to the genus Pestivirus and is the causative agent of classical swine fever, a haemorrhagic disease of pigs. The virus replicates in host cells without activating interferon (IFN) production and has been reported to be an antagonist of double-stranded RNA-induced apoptosis. The N-terminal protease (N(pro)) of CSFV is responsible for this evasion of the host innate immune response. In order to identify cellular proteins that interact with the N(pro) product of CSFV, a yeast two-hybrid screen of a human library was carried out, which identified IkappaBalpha, the inhibitor of NF-kappaB, a transcription factor involved in the control of apoptosis, the immune response and IFN production. The N(pro)-IkappaBalpha interaction was confirmed using yeast two-hybrid analysis and additional co-precipitation assays. It was also shown that N(pro) localizes to both the cytoplasmic and nuclear compartments in stably transfected cells and in CSFV-infected cells. Following stimulation by tumour necrosis factor alpha, PK-15 cell lines expressing N(pro) exhibited transient nuclear accumulation of pIkappaBalpha, but no effect of CSFV infection on IkappaBalpha localization or NF-kappaB p65 activation was observed.