Hsa_circ_0007321 regulates Zika virus replication through miR-492/NFKBID/NF-κB signaling pathway.

Hsa_circ_0007321 regulates Zika virus replication through miR-492/NFKBID/NF-κB signaling pathway.
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Hsa_circ_0007321通过miR-492/NFKBID/NF-κB信号通路调控寨卡病毒复制。

DOI:
10.1128/jvi.01232-23
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发表时间:
2023-12-21
影响因子:
5.4
通讯作者:
--
中科院分区:
医学2区
文献类型:
--
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环状RNA(CircRNA)已被证明在调节病毒感染和复制中起关键作用。我们进行了RNA测序,以鉴定在有和没有寨卡病毒(ZIKV)感染的A549人肺腺癌细胞中差异表达的circRNA。值得注意的是,hsa_circ_0007321在ZIKV感染后显著下调。然后,我们探索了hsa_circ_0007321在ZIKV复制调节中的作用和机制。Hsa_circ_0007321,来源于DIS 3L 2(DIS 3 like 3 '-5'核糖核酸外切酶2)基因的外显子2、3、4和5,主要富集在细胞质中。我们发现hsa_circ_0007321的敲低显著增加了microRNA-492水平以降低NF KBID(NF κ B抑制剂δ)表达,导致核因子-κB(NF-κB)信号传导途径的激活、炎性细胞因子的产生以及随后的ZIKV复制的抑制。这些发现说明hsa_circ_0007321作为竞争性内源RNA,通过miR-492/NFKBID NF-κB信号传导途径调节ZIKV复制。在过去的十年中,越来越多的证据表明,环状RNA(circRNA)在病毒感染和宿主抗病毒反应中起着重要的调节作用。然而,关于circRNA在寨卡病毒(ZIKV)感染中的作用的报道有限。在这项研究中,我们通过RNA测序在ZIKV感染的A549细胞中鉴定了45种差异表达的circRNA。我们阐明了下调的circRNA hsa_circ_0007321通过靶向miR-492和下游基因NFKBID来调节ZIKV复制。NFKBID是核因子-κB(NF-κB)的负调节剂,并且我们发现NF-κB途径的抑制促进ZIKV复制。因此,hsa_circ_0007321通过miR-492/NFKBID/NF-κB信号传导途径对ZIKV复制发挥其调节作用的这一发现对于开发抑制ZIKV和可能的其他病毒感染的策略具有意义。
Circular RNAs (CircRNAs) have been shown to play a critical role in regulating viral infection and replication. We performed RNA sequencing to identify differentially expressed circRNAs in A549 human lung adenocarcinoma cells with and without Zika virus (ZIKV) infection. Notably, hsa_circ_0007321 was significantly downregulated after ZIKV infection. We then explored the role and mechanism of hsa_circ_0007321 in the regulation of ZIKV replication. Hsa_circ_0007321, derived from exons 2, 3, 4, and 5 of the DIS3L2 (DIS3 like 3'−5' exoribonuclease 2) gene, was mainly enriched in cytoplasm. We found that the knockdown of hsa_circ_0007321 significantly increased microRNA-492 levels to decrease NFKBID (NFKB inhibitor delta) expression, leading to the activation of the nuclear factor-κB (NF-κB) signaling pathway, inflammatory cytokine production, and subsequently, inhibition of ZIKV replication. These findings illustrate that hsa_circ_0007321 acts as a competitive endogenous RNA that regulates ZIKV replication through the miR-492/NFKBID NF-κB signaling pathway. Over the past decade, increasing evidence has shown that circular RNAs (circRNAs) play important regulatory roles in viral infection and host antiviral responses. However, reports on the role of circRNAs in Zika virus (ZIKV) infection are limited. In this study, we identified 45 differentially expressed circRNAs in ZIKV-infected A549 cells by RNA sequencing. We clarified that a downregulated circRNA, hsa_circ_0007321, regulates ZIKV replication through targeting of miR-492 and the downstream gene NFKBID. NFKBID is a negative regulator of nuclear factor-κB (NF-κB), and we found that inhibition of the NF-κB pathway promotes ZIKV replication. Therefore, this finding that hsa_circ_0007321 exerts its regulatory role on ZIKV replication through the miR-492/NFKBID/NF-κB signaling pathway has implications for the development of strategies to suppress ZIKV and possibly other viral infections.
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