首页|Classical swine fever virus NS5A protein antagonizes innate immune response by inhibiting the NF-κB signaling
Classical swine fever virus NS5A protein antagonizes innate immune response by inhibiting the NF-κB signaling
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The NS5A non-structural protein of classical swine fever virus(CSFV)is a multifunctional protein involved in viral genomic replication,protein translation,assembly of infectious virus particles,and regulation of cellular signaling pathways.Previous report showed that NS5A inhibited nuclear factor kappa B(NF-κB)signaling induced by poly(I:C);however,the mechanism involved has not been elucidated.Here,we reported that NS5A directly interacted with NF-κB essential modulator(NEMO),a regulatory subunit of the IκB kinase(IKK)complex,to inhibit the NF-κB signaling pathway.Further investigations showed that the zinc finger domain of NEMO and the aa 126-250 segment of NS5A are essential for the interaction between NEMO and NS5A.Mechanistic analysis revealed that NS5A mediated the proteasomal degradation of NEMO.Ubiquitination assay showed that NS5A induced the K27-linked but not the K48-linked polyubiquitination of NEMO for proteasomal degradation.In addition,NS5A blocked the K63-linked polyubiquitination of NEMO,thus inhibiting IKK phosphorylation,IκBαdegradation,and NF-κB activation.These findings revealed a novel mechanism by which CSFV inhibits host innate immunity,which might guide the drug design against CSFV in the future.
Jinfu Sun、Jiaying Li、Liming Li、Haixiao Yu、Ping Ma、Yingnan Wang、Jinqi Zhu、Zezhong Feng、Changchun Tu
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Key Laboratory of Bioresource Research and Development of Liaoning Province,College of Life and Health Sciences,Northeastern University,Shenyang,110169,China
Changchun Veterinary Research Institute,Chinese Academy of Agricultural Sciences,Changchun,130122,China
Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonoses,Yangzhou University,Yangzhou,225009,China
National Nature Science Foundation of ChinaConstruction Project of Liaoning Provincial Key Laboratory,China
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