长非编码RNA lnc-ALVE1-AS1抑制ALV-J在鸡巨噬细胞中增殖  

Long Non-coding RNA lnc-AlVE1-AS1 Inhibits the Proliferation of AlV-J in Chicken Macrophages

作　　者：柴文娴 骆欢 金松 王姣 罗坚强 洪雅琴 耿拓宇[2,3] 崔恒宓 胡序明[2,3] CHAI Wenxian;LUO Huan;JIN Song;WANG Jiao;LUO Jianqiang;HONG Yaqin;GENG Tuoyu;CUI Hengmi;HU Xuming(Changzhou Animal Disease Prevention and Control Center,Changzhou 213002,China;Institute of Epigenetics and Epigenomics,College of Animal Science and Technology,Yangzhou University,Yangzhou 225009,China;Joint International Research Laboratory of Agricultural&Agri-Product Safety,Ministry of Education of China,Yangzhou University,Yangzhou 225009,China)

机构地区：[1]常州市动物疫病预防控制中心,常州213002 [2]扬州大学动物科学与技术学院/表观遗传学及表观基因组学研究所,扬州225009 [3]扬州大学教育部农业与农产品安全国际合作联合实验室,扬州225009

出　　处：《中国动物传染病学报》2024年第1期18-25,共8页Chinese Journal of Animal Infectious Diseases

基　　金：常州市科学技术局重点项目(CE20202033);国家自然科学基金(31602032);国家自然科学基金重大研究计划(91540117);江苏省畜牧学优势学科项目。

摘　　要：研究表明,源自内源性反转录病毒的长非编码RNA可能是巨噬细胞抗病毒免疫反应的重要组成部分。鸡内源性反转录病毒衍生的长非编码RNA lnc-ALVE1-AS1与宿主遗传抗性有关,能够激活非免疫细胞抗病毒天然免疫反应。为进一步探讨lnc-ALVE1-AS1在鸡巨噬细胞中的抗病毒作用及其机制,本研究通过荧光定量PCR发现lnc-ALVE1-AS1在ALV-J感染鸡巨噬细胞系HD11后24 h显著下调。进一步通过lnc-ALVE1-AS1过表达实验证实,lnc-ALVE1-AS1可以显著抑制ALV-J在HD11细胞中增殖。机制上,lnc-ALVE1-AS1显著上调HD11细胞dsRNA识别受体(TLR3)、Ⅰ型干扰素(IFN-α和IFN-β)和其他抗病毒天然免疫基因(IRF7、MX1、OASL和IFITM3)表达。然而,干扰TLR3或者抑制TLR3信号后lnc-ALVE1-AS1诱导Ⅰ型干扰素(IFN-α和IFN-β)的能力显著减弱。共聚焦定位分析显示在HD11细胞中lnc-ALVE1-AS1可以与TLR3蛋白直接结合。这说明激活TLR3信号可能是lnc-ALVE1-AS1抑制ALV-J在巨噬细胞中增殖的一个重要机制。本研究揭示了lnc-ALVE1-AS1在巨噬细胞中抗病毒功能及其作用机制,为抗病育种研究提供了新的遗传基础。Previous studies have shown that long non-coding RNAs derived from Endogenous retroviruses may be an important part of the antiviral immune response in macrophages.It has been reported that the long non-coding RNA lnc-ALVE1-AS1derived from chicken Endogenous retrovirus is related to host genetic resistance and can activate the antiviral innate immunity of non-immune cells.In order to further explore the antiviral effect oflnc-ALVE1-AS1in chicken macrophages and its mechanism,chicken macrophage cell line HD11 was infected with ALV-J and lnc-ALVE1-AS1 was found to be significantly down-regulated at 24 h as tested using the fluorescence quantitative PCR.Overexpression experiments further confirmed thatlnc-ALVE1-AS1significantly inhibited the proliferation of ALV-J in HD11 cells.The mechanism was reflected by the fact thatlnc-ALVE1-AS1significantly upregulated the expression of dsRNA recognition receptor(TLR3),type I interferons(IFN-αand IFN-β)and other antiviral innate immune genes(IRF7,MX1,OASL and IFITM3)in HD11 cells.However,the induction of type I interferons(IFN-αand IFN-β)by lnc-ALVE1-AS1 was significantly reduced after TLR3 interference or TLR3 signals inhibition.Confocal localization analysis showed that lnc-ALVE1-AS1 directly bound to TLR3 protein in HD11 cells,suggesting that activation of TLR3 signals might be an important mechanism for lnc-ALVE1-AS1to inhibit the proliferation of ALV-J in macrophages.This study revealed the antiviral function and mechanism of lnc-ALVE1-AS1 in macrophages and provided a new genetic basis for disease resistance breeding research.

关 键 词：内源性反转录病毒 lnc-ALVE1-AS1 禽白血病病毒 鸡巨噬细胞 

分 类 号：S852.4[农业科学—基础兽医学]