首页|长非编码RNAlnc-ALVE1-AS1抑制ALV-J在鸡巨噬细胞中增殖

长非编码RNAlnc-ALVE1-AS1抑制ALV-J在鸡巨噬细胞中增殖

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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-a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-a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。
Long Non-coding RNA lnc-AlVE1-AS1 Inhibits the Proliferation of A1V-J in Chicken Macrophages
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-AS1 derived 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 of lnc-ALVE1-AS1 in chicken macrophages and its mechanism,chicken macrophage cell line HD 11 was infected with ALV-J and lnc-ALVE1-ASl was found to be significantly down-regulated at 24 h as tested using the fluorescence quantitative PCR.Overexpression experiments further confirmed that lnc-ALVE1-AS1 significantly inhibited the proliferation of ALV-J in HD11 cells.The mechanism was reflected by the fact that lnc-ALVE1-AS1 significantly upregulated the expression of dsRNA recognition receptor(TLR3),type I interferons(IFN-α and IFN-β)and other antiviral innate immune genes(IRF7,MX1,OASL and IFITM3)in HD11 cells.However,the induction of type Ⅰ interferons(IFN-α and 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-AS1 to 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.

Endogenous retroviruseslnc-ALVE1-AS1Avian leukosis viruschicken macrophages

柴文娴、骆欢、金松、王姣、罗坚强、洪雅琴、耿拓宇、崔恒宓、胡序明

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常州市动物疫病预防控制中心,常州 213002

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

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

内源性反转录病毒 lnc-ALVE1-AS1 禽白血病病毒 鸡巨噬细胞

常州市科技局重点项目国家自然科学基金国家自然科学基金重大研究计划江苏省畜牧学优势学科建设项目

CE202020333160203291540117

2024

中国动物传染病学报
中国农业科学院上海兽医研究所

中国动物传染病学报

CSTPCD北大核心
影响因子:0.651
ISSN:1674-6422
年,卷(期):2024.32(1)
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