Classical swine fever virus NS5A protein antagonizes innate immune response by inhibiting the NF-xB signaling

文献类型： 外文期刊

第一作者： Sun, Jinfu

作者： Sun, Jinfu;Li, Jiaying;Li, Liming;Yu, Haixiao;Ma, Ping;Wang, Yingnan;Zhu, Jinqi;Feng, Zezhong;Tu, Changchun;Tu, Changchun

作者机构：

关键词： Classical swine fever virus (CSFV); NS5A; NF-xB signaling; NEMO; Polyubiquitination; Proteasomal degradation

期刊名称：VIROLOGICA SINICA （ 影响因子：5.5； 五年影响因子：4.9 ）

ISSN： 1674-0769

年卷期： 2023 年 38 卷 6 期

页码：

收录情况： SCI

摘要： 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-xB) signaling induced by poly(I:C); however, the mechanism involved has not been elucidated. Here, we reported that NS5A directly interacted with NF-xB essential modulator (NEMO), a regulatory subunit of the IxB kinase (IKK) complex, to inhibit the NF-xB 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, IxBa degradation, and NF-xB 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.

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