An interferon-stimulated long non-coding RNA USP30-AS1 as an immune modulator in influenza A virus infection.

IF 5.5 1区 医学 Q1 MICROBIOLOGY PLoS Pathogens Pub Date : 2025-01-08 eCollection Date: 2025-01-01 DOI:10.1371/journal.ppat.1012854
Yi Cao, Alex W H Chin, Haogao Gu, Mengting Li, Yuner Gu, Sylvia P N Lau, Kenrie P Y Hui, Michael C W Chan, Leo L M Poon
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Abstract

Long non-coding RNAs (lncRNAs) are essential components of innate immunity, maintaining the functionality of immune systems that control virus infection. However, how lncRNAs engage immune responses during influenza A virus (IAV) infection remains unclear. Here, we show that lncRNA USP30-AS1 is up-regulated by infection of multiple different IAV subtypes and is required for tuning inflammatory and antiviral response in IAV infection. Genetically inactivation of USP30-AS1 enhances viral protein synthesis and viral growth. USP30-AS1 is an interferon-stimulated gene, and the induction of USP30-AS1 can be achieved by JAK-STAT mediated signaling activation. The immune regulation of USP30-AS1 is independent of its proximal protein-coding gene USP30. In IAV infection, deletion of USP30-AS1 unleashes high systemic inflammatory responses involving a broad range of pro-inflammatory factors, suggesting USP30-AS1 as a critical modulator of immune responses in IAV infection. Furthermore, we established a database providing well-annotated host gene expression profiles IAV infection or immune stimulation.

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干扰素刺激的长链非编码RNA USP30-AS1在甲型流感病毒感染中的免疫调节剂作用
长链非编码rna (lncrna)是先天免疫的重要组成部分,维持控制病毒感染的免疫系统的功能。然而,在甲型流感病毒(IAV)感染过程中,lncrna如何参与免疫反应仍不清楚。在这里,我们发现lncRNA USP30-AS1在多种不同的IAV亚型感染中上调,并且在IAV感染中调节炎症和抗病毒反应是必需的。USP30-AS1基因失活促进病毒蛋白合成和病毒生长。USP30-AS1是干扰素刺激基因,USP30-AS1的诱导可以通过JAK-STAT介导的信号激活来实现。USP30- as1的免疫调控独立于其近端蛋白编码基因USP30。在IAV感染中,USP30-AS1的缺失引发了涉及广泛促炎因子的高全身性炎症反应,表明USP30-AS1是IAV感染中免疫反应的关键调节剂。此外,我们建立了一个数据库,提供在病毒感染或免疫刺激下的宿主基因表达谱。
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来源期刊
PLoS Pathogens
PLoS Pathogens MICROBIOLOGY-PARASITOLOGY
自引率
3.00%
发文量
598
期刊介绍: Bacteria, fungi, parasites, prions and viruses cause a plethora of diseases that have important medical, agricultural, and economic consequences. Moreover, the study of microbes continues to provide novel insights into such fundamental processes as the molecular basis of cellular and organismal function.
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