长链非编码RNA-RPS6P3抑制甲型流感病毒复制并减弱NS1对天然免疫反应的抑制作用。

Lnc-RPS6P3 Inhibits Influenza A Virus Replication and Attenuates the Inhibitory Effect of NS1 on Innate Immune Response.

作者信息

Wang Mingge, Yao Xinli, Tong Xiaomei, Qi Dandan, Ye Xin

机构信息

School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China.

Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China.

出版信息

Microorganisms. 2024 Mar 26;12(4):654. doi: 10.3390/microorganisms12040654.

DOI:10.3390/microorganisms12040654

PMID:38674599

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11052439/

Abstract

Host factors play important roles in influenza A virus (IAV) replication. In order to identify novel host factors involved in IAV replication, we compared the differentially expressed genes in A549 cells after IAV infection. We found that lncRNA lnc-RPS6P3 was up-regulated upon viral infection and poly(I:C) and IFN-β treatment, indicating it was an interferon-stimulated gene. Functional analysis demonstrated that overexpression of lnc-RPS6P3 inhibited IAV replication while knockdown of lnc-RPS6P3 promoted viral infection in A549 cells. Lnc-RPS6P3 inhibited both transcription and replication of IAV. Further study showed that lnc-RPS6P3 interacted with viral NP and interfered with NP self-oligomerization and, consequently, inhibited vRNP activity. In addition, lnc-RPS6P3 interacted with viral NS1 and reduced the interaction of NS1 and RIG-I; it also attenuated the inhibitory effect of NS1 on IFN-β stimulation. In conclusion, we revealed that lnc-RPS6P3 is an interferon-stimulated gene that inhibits IAV replication and attenuates the inhibitory effect of NS1 on innate immune response.

摘要

宿主因素在甲型流感病毒（IAV）复制中发挥重要作用。为了鉴定参与IAV复制的新型宿主因素，我们比较了IAV感染后A549细胞中差异表达的基因。我们发现lncRNA lnc-RPS6P3在病毒感染以及聚肌苷酸-聚胞苷酸（poly(I:C)）和干扰素-β（IFN-β）处理后上调，表明它是一种干扰素刺激基因。功能分析表明，lnc-RPS6P3的过表达抑制IAV复制，而敲低lnc-RPS6P3则促进A549细胞中的病毒感染。lnc-RPS6P3抑制IAV的转录和复制。进一步研究表明，lnc-RPS6P3与病毒核蛋白（NP）相互作用，干扰NP的自我寡聚化，从而抑制病毒核糖核蛋白（vRNP）活性。此外，lnc-RPS6P3与病毒非结构蛋白1（NS1）相互作用，减少NS1与维甲酸诱导基因I（RIG-I）的相互作用；它还减弱了NS1对IFN-β刺激的抑制作用。总之，我们揭示了lnc-RPS6P3是一种干扰素刺激基因，可抑制IAV复制并减弱NS1对先天免疫反应的抑制作用。