Regulation of influenza A virus infection by Lnc-PINK1-2:5.

Regulation of influenza A virus infection by Lnc-PINK1-2:5.
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DOI:
10.1111/jcmm.17249
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发表时间:
2022-04
影响因子:
5.3
通讯作者:
Liu L
Liu L
中科院分区:
医学2区
文献类型:
--
作者:
Pushparaj S;Zhu Z;Huang C;More S;Liang Y;Lin K;Vaddadi K;Liu L

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流感病毒每年在全世界造成约291,000至646,000人死亡。它也是一种重要的人畜共患疾病,影响猪、马和鸟类等动物。尽管疫苗接种被用来预防流感病毒感染,但治疗这种疾病的选择有限。长链非编码RNA(lncRNA)是指不翻译成蛋白质的200多个核苷酸的RNA分子。它们在生理和病理过程中起着重要作用。在这项研究中,我们发现了一种新的转录本Lnc‐ PINK 1 ‐2:5,它被流感病毒上调。这种lncRNA主要位于细胞核中,不受I型干扰素的影响。Lnc‐ PINK 1 ‐2:5的过表达降低了细胞中流感病毒mRNA和蛋白水平以及培养基中的滴度。使用CRISPR干扰敲低Lnc-PINK 1 - 2:5增强了病毒复制。Lnc‐ PINK 1 ‐2:5的抗病毒活性不依赖于流感病毒株。RNA测序分析显示,在流感病毒感染期间,Lnc‐ PINK 1 ‐2:5上调硫氧还蛋白相互作用蛋白(TXNIP)。TXNIP的过表达降低了流感病毒的感染,表明TXNIP是一种抗病毒基因。TXNIP的敲低消除了Lnc‐ PINK 1 ‐2:5‐介导的流感病毒感染增加。总之,新鉴定的Lnc-PINK 1 - 2:5同种型是一种通过上调TXNIP基因表达起作用的抗流感lncRNA。
Influenza virus causes approximately 291,000 to 646,000 human deaths worldwide annually. It is also a disease of zoonotic importance, affecting animals such as pigs, horses, and birds. Even though vaccination is being used to prevent influenza virus infection, there are limited options available to treat the disease. Long noncoding RNAs (lncRNAs) are RNA molecules with more than 200 nucleotides that do not translate into proteins. They play important roles in the physiological and pathological processes. In this study, we identified a novel transcript, Lnc‐PINK1‐2:5 that was upregulated by influenza virus. This lncRNA was predominantly located in the nucleus and was not affected by type I interferons. Overexpression of Lnc‐PINK1‐2:5 reduced the influenza viral mRNA and protein levels in cells as well as titres in culture media. Knockdown of Lnc‐PINK1‐2:5 using CRISPR interference enhanced the virus replication. Antiviral activity of Lnc‐PINK1‐2:5 was independent of influenza virus strains. RNA sequencing analysis revealed that Lnc‐PINK1‐2:5 upregulated thioredoxin interacting protein (TXNIP) during influenza virus infection. Overexpression of TXNIP reduced influenza virus infection, suggesting that TXNIP is an antiviral gene. Knockdown of TXNIP abolished the Lnc‐PINK1‐2:5‐mediated increase in influenza virus infection. In conclusion, the newly identified Lnc‐PINK1‐2:5 isoform is an anti‐influenza lncRNA acting through the upregulation of TXNIP gene expression.
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