PDF(Pubmed)
Abstract：
Pseudorabies virus (PRV) has evolved multiple strategies to evade host antiviral responses to benefit virus replication and establish persistent infection. Recently, tripartite motif 26 (TRIM26), a TRIM family protein, has been shown to be involved in a broad range of biological processes involved in innate immunity, especially in regulating viral infection. Herein, we found that the expression of TRIM26 was significantly induced after PRV infection. Surprisingly, the overexpression of TRIM26 promoted PRV production, while the depletion of this protein inhibited virus replication, suggesting that TRIM26 could positively regulate PRV infection. Further analysis revealed that TRIM26 negatively regulates the innate immune response by targeting the RIG-I-triggered type I interferon signalling pathway. TRIM26 was physically associated with MAVS independent of viral infection and reduced MAVS expression. Mechanistically, we found that NDP52 interacted with both TRIM26 and MAVS and that TRIM26-induced MAVS degradation was almost entirely blocked in NDP52-knockdown cells, demonstrating that TRIM26 degrades MAVS through NDP52-mediated selective autophagy. Our results reveal a novel mechanism by which PRV escapes host antiviral innate immunity and provide insights into the crosstalk among virus infection, autophagy, and the innate immune response.
摘要：
伪狂犬病病毒（PRV）已经进化出多种策略来逃避宿主的抗病毒反应，以促进病毒复制并建立持续感染。最近,三方主题26(TRIM26)，TRIM家族蛋白，已被证明参与了广泛的生物学过程，涉及先天免疫，尤其是在调节病毒感染方面。在这里，我们发现PRV感染后TRIM26的表达被显著诱导。令人惊讶的是,TRIM26的过表达促进了PRV的产生，这种蛋白质的消耗抑制了病毒的复制，提示TRIM26可以正向调节PRV感染。进一步的分析显示,TRIM26通过靶向RIG-I触发的I型干扰素信号通路负调节先天免疫应答。TRIM26与MAVS物理相关，与病毒感染无关，MAVS表达降低。机械上,我们发现NDP52与TRIM26和MAVS相互作用，TRIM26诱导的MAVS降解在NDP52敲低细胞中几乎完全被阻断，证明TRIM26通过NDP52介导的选择性自噬降解MAVS。我们的结果揭示了PRV逃避宿主抗病毒先天免疫的新机制，并提供了对病毒感染之间串扰的见解。自噬,和先天免疫反应。
