一种新型长链非编码RNA SAAL通过促进先天免疫反应抑制甲型流感病毒复制。

A Novel lncRNA SAAL Suppresses IAV Replication by Promoting Innate Responses.

作者信息

Liu Qingzheng, Yang Hongjun, Zhao Lingcai, Huang Nan, Ping Jihui

机构信息

MOE Joint International Research Laboratory of Animal Health and Food Safety, Engineering Laboratory of Animal Immunity of Jiangsu Province, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China.

Key Laboratory of Livestock and Poultry Multi-Omics of MARA, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan 250100, China.

出版信息

Microorganisms. 2022 Nov 25;10(12):2336. doi: 10.3390/microorganisms10122336.

DOI:10.3390/microorganisms10122336

PMID:36557591

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9785332/

Abstract

Influenza A virus (IAV) infection has traditionally been a serious problem in animal husbandry and human public health security. Recently, many studies identified that long noncoding RNAs play an important role in the antiviral immune response after the infection of the influenza virus. However, there are still lots of IAV-related lncRNAs that have not been well-characterized. Using RNA sequencing analysis, we identified a lncRNA, named Serpina3i Activation Associated lncRNA (SAAL), which can be significantly upregulated in mice after IAV infection. In this study, we found that overexpression of SAAL inhibited the replication of A/WSN/33(WSN). SAAL upregulated Serpina3i with or without WSN infection. Overexpression of Serpina3i reduced influenza virus infection. Meanwhile, knockdown of Serpina3i enhanced the replication of WSN. Furthermore, knockdown of Serpina3i abolished the SAAL-mediated decrease in WSN infection. Overexpression of SAAL or Serpina3i positively regulated the transcription of interferon β (IFN-β) and several critical ISGs after WSN infection. In conclusion, we found that the novel lncRNA SAAL is a critical anti-influenza regulator by upregulating the mRNA level of Serpina3i.

摘要

甲型流感病毒（IAV）感染一直是畜牧业和人类公共卫生安全方面的严重问题。最近，许多研究表明，长链非编码RNA在流感病毒感染后的抗病毒免疫反应中发挥重要作用。然而，仍有许多与IAV相关的长链非编码RNA尚未得到充分表征。通过RNA测序分析，我们鉴定出一种名为丝氨酸蛋白酶抑制剂3i激活相关长链非编码RNA（SAAL）的长链非编码RNA，其在IAV感染后的小鼠中可显著上调。在本研究中，我们发现SAAL的过表达抑制了A/WSN/33（WSN）的复制。无论是否感染WSN，SAAL均可上调丝氨酸蛋白酶抑制剂3i。丝氨酸蛋白酶抑制剂3i的过表达减少了流感病毒感染。同时，敲低丝氨酸蛋白酶抑制剂3i增强了WSN的复制。此外，敲低丝氨酸蛋白酶抑制剂3i消除了SAAL介导的WSN感染减少。SAAL或丝氨酸蛋白酶抑制剂3i的过表达在WSN感染后正向调节干扰素β（IFN-β）和几种关键干扰素刺激基因（ISG）的转录。总之，我们发现新型长链非编码RNA SAAL通过上调丝氨酸蛋白酶抑制剂3i的mRNA水平，是一种关键的抗流感调节因子。