Dual NDP52 Function in Persistent CSFV Infection
Dual NDP52 Function in Persistent CSFV Infection
复制标题
NDP52 在持续性 CSFV 感染中的双重功能
DOI：
10.3389/fmicb.2019.02962
复制
发表时间：
2020-01-08
影响因子：
5.2
通讯作者：
Chen, Jinding
中科院分区：
文献类型：
--
作者：
Fan, Shuangqi;Wu, Keke;Chen, Jinding
病毒已经进化出许多机制来逃避宿主的抗病毒反应。以前，我们发现猪瘟病毒（CSFV）感染诱导自噬使用自噬体作为自我复制位点，从而逃避宿主免疫反应，促进长期感染。然而，CSFV进入自噬体的潜在机制以及自噬促进病毒复制的机制仍不清楚。我们发现CSFV感染抑制自噬受体核点蛋白52 kDa（NDP 52）的表达、遍在蛋白化和SUMO 2 -4修饰。进一步的分析表明，CSFV通过Pten诱导的激酶1（PINK 1）-Parkin介导了NDP 52的泛素化和SUMO化。此外，NDP 52抑制还抑制CSFV复制和诱导线粒体自噬标记蛋白的表达。NDP 52的抑制降低了CD 63的表达和与CSFV E2蛋白的结合，这在CSFV持续感染中具有重要作用。由于NDP 52与NF-κ B B天然免疫途径密切相关，在抗病毒应答中起重要作用，因此我们研究了NDP 52是否通过释放免疫因子和抗病毒信号抑制猪瘟病毒复制。我们的研究结果表明，抑制NDP 52促进干扰素和TNF的释放，并促进NF-κ B通路的激活。总之，我们发现NDP 52抑制不仅减少CSFV结合和进入自噬囊泡，而且通过活性NF-κ B抗病毒免疫途径抑制CSFV复制。我们的数据揭示了一种新的机制，NDP 52，自噬受体，介导CSFV感染，并提供了新的抗病毒策略的发展途径。
Viruses have evolved many mechanisms to escape host antiviral responses. Previously, we found that classical swine fever virus (CSFV) infection induces autophagy using the autophagosome as a self-replication site, thereby evading the host immune response and promoting long-term infection. However, the underlying mechanisms used by CSFV to enter autophagosomes and the mechanism by which autophagy promotes viral replication remain unclear. We found that CSFV infection inhibited autophagy receptor nuclear dot protein 52 kDa (NDP52) expression, ubiquitination, and SUMO2-4 modification. Further analyses revealed that CSFV mediated ubiquitination and SUMOylation of NDP52 via Pten-induced kinase 1 (PINK1)-Parkin. Moreover, NDP52 inhibition also inhibited CSFV replication and the induction of mitophagy marker proteins expression. Inhibition of NDP52 reduced CD63 expression and binding to CSFV E2 protein, which has an essential role in persistent CSFV infection. As NDP52 has a close relationship with the NF-kappa B innate immunity pathway and plays an important role in the antiviral response, we investigated whether NDP52 inhibited CSFV replication through the release of immune factors and antivirus signals. Our results showed that inhibiting NDP52 boosted interferon and TNF release and promoted NF-kappa B pathway activation. In summary, we found that NDP52 inhibition not only reduces CSFV binding and entry into autophagic vesicles, but also inhibits CSFV replication by active NF-kappa B antiviral immune pathways. Our data reveal a novel mechanism by which NDP52, an autophagy receptor, mediates CSFV infection, and provide new avenues for the development of antiviral strategies.