Shenzhen Institute of Wuhan University, Shenzhen, China.
Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
Intervirology. 2021;64(3):147-155. doi: 10.1159/000515903. Epub 2021 May 5.
Enterovirus 71 (EV71) infects millions of children every year in China and has become a challenge to public health. However, there is no effective treatment for EV71 infection. Long noncoding RNAs (lncRNAs) have been found to play various roles in virus replication and infection.
We aimed to explore the role of a novel long noncoding RNA AK097647 (lncRNA-AK097647) during EV71 infection.
To assess the role of lncRNA-AK097647 during EV71 infection, siRNAs were used to silence lncRNA-K097647 expression. RT-qPCR assay and Western blotting were applied to measure the mRNA and protein levels of EV71 VP1 and the phosphorylation of NF-κB. ELISA was used to detect the level of IFN-λ1 expression.
The novel lncRNA-AK097647 was upregulated in human rhabdomyosarcoma cells and the blood of hand, foot, and mouth disease patients infected with EV71, as demonstrated by RT-qPCR. Interestingly, RNAi-mediated knockdown of lncRNA-AK097647 dramatically increased the level of IFN-λ1 expression, resulting in the suppression of EV71 replication. In contrast, overexpression of lncRNA-AK097647 decreased the level of IFN-λ1 expression and resulted in increased EV71 replication. In addition, we found that lncRNA-AK097647 could inhibit the phosphorylation of NF-κB.
These results suggest a novel mechanism by which EV71 evades the IFN-mediated host antiviral response by increasing lncRNA-AK097647 expression.
肠道病毒 71 型（EV71）每年在中国感染数百万儿童，已成为公共卫生的挑战。然而，目前还没有针对 EV71 感染的有效治疗方法。长链非编码 RNA（lncRNA）已被发现在病毒复制和感染中发挥多种作用。
本研究旨在探讨新型长链非编码 RNA AK097647（lncRNA-AK097647）在 EV71 感染中的作用。
为了评估 lncRNA-AK097647 在 EV71 感染过程中的作用，我们使用 siRNA 沉默 lncRNA-AK097647 的表达。应用 RT-qPCR 测定和 Western blot 检测 EV71 VP1 的 mRNA 和蛋白水平以及 NF-κB 的磷酸化水平。采用 ELISA 检测 IFN-λ1 的表达水平。
通过 RT-qPCR 证实，新型 lncRNA-AK097647 在人横纹肌肉瘤细胞和感染 EV71 的手足口病患者的血液中呈上调表达。有趣的是，RNAi 介导的 lncRNA-AK097647 敲低显著增加了 IFN-λ1 的表达水平，从而抑制了 EV71 的复制。相反，lncRNA-AK097647 的过表达降低了 IFN-λ1 的表达水平，导致 EV71 的复制增加。此外，我们发现 lncRNA-AK097647 可以抑制 NF-κB 的磷酸化。
这些结果表明，EV71 通过增加 lncRNA-AK097647 的表达来逃避 IFN 介导的宿主抗病毒反应，这是一种新的机制。
