关键词: IBDV PRMT3 chicken facilitate interferon-β

来  源:   DOI:10.1016/j.psj.2024.103989   PDF(Pubmed)

Abstract:
Protein arginine methyltransferases (PRMTs) in mammals play a role in various signaling pathways, such as virus infection, inflammasome responses, and cancer growth. While some PRMTs have been found to regulate interferon production in mammals, the mechanism in chickens remains to be fully understood. This study focused on investigating the function of chicken PRMTs. Our findings indicate that chicken PRMTs act as inhibitors of interferon production in response to dsRNA or MDA5 stimulation. Each PRMT is involved in different stages of interferon induction through the MDA5-MAVS-TBK1 pathway. Furthermore, we observed the colocalization of multiple PRMTs with the viral protein VP3 of infectious bursal disease virus (IBDV). Among the chicken PRMTs studied, PRMT3 was found to be widely expressed in various organs and its expression was upregulated during IBDV infection. Notably, PRMT3 supported IBDV replication, as demonstrated by ectopic expression and inhibition studies using SGC-707. Silencing of PRMT3 led to enhanced interferon production and inhibition of IBDV replication. This study provides novel insights into the role of chicken PRMTs, particularly PRMT3, in promoting IBDV replication by suppressing interferon signaling.
摘要:
蛋白质精氨酸甲基转移酶(PRMTs)在哺乳动物的各种信号通路中发挥作用,如病毒感染,炎症反应,和癌症生长。虽然已经发现一些PRMT在哺乳动物中调节干扰素的产生,鸡的机制还有待充分理解。本研究旨在研究鸡PRMTs的功能。我们的发现表明,鸡PRMT在响应dsRNA或MDA5刺激时充当干扰素产生的抑制剂。每个PRMT通过MDA5-MAVS-TBK1途径参与干扰素诱导的不同阶段。此外,我们观察到多个PRMT与传染性法氏囊病病毒(IBDV)的病毒蛋白VP3的共定位。在研究的鸡肉PRMT中,发现PRMT3在各种器官中广泛表达,并且在IBDV感染期间其表达上调。值得注意的是,PRMT3支持的IBDV复制,如使用SGC-707的异位表达和抑制研究所证明的。PRMT3的沉默导致干扰素产生增强和IBDV复制抑制。这项研究为鸡PRMT的作用提供了新的见解,特别是PRMT3,通过抑制干扰素信号传导来促进IBDV复制。
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