• 《中国科学引文数据库(CSCD)》来源期刊
  • 中国科技期刊引证报告(核心版)期刊
  • 《中文核心期刊要目总览》核心期刊
  • RCCSE中国核心学术期刊

蓝舌病病毒利用泛素−蛋白酶体系统调控视黄酸诱导基因I信号传导

鲁丹枫, 张振兴, 李占鸿, 朱沛, 李卓然

鲁丹枫, 张振兴, 李占鸿, 等. 蓝舌病病毒利用泛素−蛋白酶体系统调控视黄酸诱导基因I信号传导[J]. 华南农业大学学报, 2025, 46(4): 480-491. DOI: 10.7671/j.issn.1001-411X.202412036
引用本文: 鲁丹枫, 张振兴, 李占鸿, 等. 蓝舌病病毒利用泛素−蛋白酶体系统调控视黄酸诱导基因I信号传导[J]. 华南农业大学学报, 2025, 46(4): 480-491. DOI: 10.7671/j.issn.1001-411X.202412036
LU Danfeng, ZHANG Zhenxing, LI Zhanhong, et al. Bluetongue virus regulates retinoic acid inducible gene I signal transduction through the ubiquitin-proteasome system[J]. Journal of South China Agricultural University, 2025, 46(4): 480-491. DOI: 10.7671/j.issn.1001-411X.202412036
Citation: LU Danfeng, ZHANG Zhenxing, LI Zhanhong, et al. Bluetongue virus regulates retinoic acid inducible gene I signal transduction through the ubiquitin-proteasome system[J]. Journal of South China Agricultural University, 2025, 46(4): 480-491. DOI: 10.7671/j.issn.1001-411X.202412036

蓝舌病病毒利用泛素−蛋白酶体系统调控视黄酸诱导基因I信号传导

基金项目: 

云南省万人计划青年拔尖人才专项(YNWR-QNBJ-2020-211);国家自然科学基金(32360883,32460889);云南省热带亚热带动物病毒病重点实验室开放课题(2024RW002)

详细信息
    作者简介:

    鲁丹枫,主要从事动物虫媒病毒研究,E-mail: ldf3129554@163.com

    通讯作者:

    李卓然,主要从事动物虫媒病毒研究,E-mail: lizhuoran85@126.com

  • 中图分类号: S855.3

Bluetongue virus regulates retinoic acid inducible gene I signal transduction through the ubiquitin-proteasome system

  • 摘要:
    目的 

    视黄酸诱导基因I(Retinoic acid inducible gene I, RIG-I)泛素化修饰链上第48位赖氨酸(Lysine, Lys)残基连接的多泛素链能够调控RIG-I蛋白的稳定性,以防止RIG-I信号和宿主抗病毒反应的过度激活。本研究旨在探讨蓝舌病病毒(Bluetongue virus, BTV)是否也通过影响RIG-I的泛素化修饰调控其信号传导而利于自身增殖。

    方法 

    以BTV感染永生化绵羊肺动脉血管内皮(Sheep pulmonary artery endothelial cells, SPAE)细胞,分别利用蛋白酶体抑制剂MG-132和去泛素化酶(Deubiquitinase, DUB)抑制剂PR-619处理细胞,通过RT-qPCR分别检测环指蛋白125(Ring finger protein 125, RNF125)、泛素特异性蛋白酶4(Ubiquitin-specific protease 4, USP4)、RIG-I、干扰素调节因子3(Interferon regulatory factor 3, IRF3)和干扰素α(Interferon α, IFN-α)的转录水平以及BTV基因组拷贝数;利用免疫印迹(Western blotting)和ELISA检测以上蛋白的表达水平;采用免疫荧光(Immunofluorescence)检测IRF3核转移水平。

    结果 

    BTV感染上调RNF125、RIG-I、IRF3和IFN-α的转录和表达水平,转录水平上调1.20~8.68倍,表达水平上调0.06~3.94倍;尽管USP4的转录水平轻微上调,但是表达水平下调。蛋白酶体抑制剂MG-132显著抑制RIG-I的降解,并导致IRF3细胞核转移率在感染后24 h(24 hour post-infection, 24 hpi)和48 hpi较未处理对应组别分别上升9.67%和8.66%,IFN-α表达水平在48 hpi上调至未处理对应组别的2.18倍,BTV基因组拷贝数在24和48 hpi分别降低至未处理对应组别的73.63%和85.37%。DUB抑制剂PR-619处理明显促进RIG-I降解,IRF3细胞核转移率在24和48 hpi较未处理对应组别分别下降8.00%和16.67%,IFN-α表达水平在24 hpi下调至未处理对应组别的56.50%,BTV基因组拷贝数在24和48 hpi分别增加至未处理对应组别的0.92和0.49倍。

    结论 

    BTV利用泛素−蛋白酶体系统(Ubiquitin-proteasome system)调控宿主RIG-I信号传导而利于自身增殖。

    Abstract:
    Objective 

    The polyubiquitin chain linked to lysine (Lys) residues at 48th position of ubiquitination modification chain of retinoic acid inducible gene I (RIG-I) regulates RIG-I protein stability to prevent over-activation of RIG-I signaling and host antiviral responses. The aim of the study was to explore whether bluetongue virus (BTV) also regulated RIG-I signaling by affecting ubiquitination modification of RIG-I for its own reproductive benefit.

    Method 

    The immortalized sheep pulmonary artery endothelial cells (SPAE) were infected with BTV, and then were treated with the proteasome inhibitor MG-132 and the deubiquitinase (DUB) inhibitor PR-619, respectively. The transcriptional levels of ring finger protein 125 (RNF125), ubiquitin-specific protease 4 (USP4), RIG-I, interferon regulatory factor 3 (IRF3), and interferon α (IFN-α), along with the genomic copy numbers of BTV were detected using RT-qPCR. The expression levels of proteins mentioned above were detected with Western blotting and ELISA. Immunofluorescence were conducted to analyze the nuclear translocation ratio of IRF3.

    Result 

    BTV infection upregulated the transcriptional levels of RNF125, RIG-I, IRF3, and IFN-α from 1.20 to 8.68-fold, and expression levels from 0.06 to 3.94-fold, respectively. Although the transcriptional level of USP4 gene slightly increased, the expression level of USP4 was downregulated. Treatment with the proteasome inhibitor MG-132 significantly suppressed RIG-I degradation induced by BTV infection; The nuclear translocation ratio of IRF3 in MG-132 treated SPAE cells increased by 9.67% and 8.66% compared with their untreated counterparts at 24 hours post-infection (24 hpi) and 48 hpi; The expression level of IFN-α increased by 2.18-fold comparing with that of the corresponding untreated group at 48 hpi; The genomic copy numbers of BTV decreased to 73.63% and 85.37% of those of the untreated counterparts at 24 and 48 hpi, respectively. Treatment with DUB inhibitor PR-619 obviously promoted RIG-I degradation; The nuclear translocation ratio of IRF3 in PR-619 treated SPAE cells decreased by 8.00% and 16.67% compared with their untreated counterparts at 24 and 48 hpi; The expression level of IFN-α decreased to 56.50% comparing with that of the corresponding untreated group at 24 hpi; The copy numbers of BTV genome increased to 0.92-fold and 0.49-fold of the untreated counterparts at 24 and 48 hpi, respectively.

    Conclusion 

    BTV utilized the ubiquitin-proteasome system (UPS) to regulate host RIG-I signaling to favor viral propagation.

  • 仔猪初生窝重是出生24 h内全部存活的猪仔体重之和。一般情况下,仔猪初生重越大,仔猪活力越强,抗病力越强[1]。仔猪初生窝重受环境因素的影响较大,尤其是母猪妊娠后期的营养措施[2]。在生产管理较为规范的猪场,仔猪初生窝重则主要受到品种、胎次等因素的影响。有研究表明:仔猪初生重为低遗传力性状,其遗传力在0.10左右[3];对猪繁殖性状的遗传改良,从结合系谱和表型信息的最佳线性无偏预测(Best linear unbiased prediction,BLUP)技术,到结合少数SNP标记信息的标记辅助选择(Marker assisted selection,MAS)技术,再到结合全基因组标记信息的BLUP(Genomic BLUP,GBLUP)技术,选择准确性逐步提高[3]。本研究采用简化基因组测序技术(Genotyping-by-sequencing,GBS)[5]和一步法BLUP(Single-step genomic BLUP,ssGBLUP)技术,对某一大白猪核心群母猪进行基因分型,并分别采用BLUP、GBLUP和ssGBLUP方法,对仔猪初生窝重的遗传估计育种值(Genomic estimated breeding value,GEBV)的选择准确性进行评估;此外,本文对初生窝重的遗传参数进行估计,旨在为仔猪初生窝重的选育提供参考。

    本研究以广东温氏种猪科技有限公司某核心场W64系大白猪为研究对象,并以该场为出生场,选取2010—2019年5月76 710条繁殖性能相关的测定记录,包括产仔数、产活仔数、健仔数、初生窝重、弱仔数、畸形仔数、死胎数和木乃伊数。其中弱差猪数为弱仔数、畸形仔数、死胎数和木乃伊数总和,用其来代表无效仔数,其与健仔数合并构成总产仔数。

    基因分型试验样品来自于该场基础母猪核心群近2年来有繁殖记录的母猪,共2 344头,采集其耳样并用75%(φ)乙醇溶液保存。

    本研究采用的简化基因组分型方法参考文献[5]。该方法采用EcoRI和MspI双内切酶对基因组进行切割,并在两端加上能够对个体识别的标签序列,通过PCR扩增和磁珠纯化,来达到富集目的片段的目的,并采用高通量二代测序技术对目标片段进行双端测序。试验流程依次包括:基因组DNA的提取和质检、基因组稀释定量、GBS文库的构建、文库质控、上机测序和测序数据分析。

    本研究利用Excel剔除缺失值和异常数据,并用Q-Q plot R程序包验证其是否服从正态分布,选取μ±3σ以内的表型数据,结合整理好的数据文件,利用DMUTrace软件追溯群体系谱,并按照DMU软件要求整理为数据文件和系谱文件;同时利用GVCBLUP和BLUPF90软件,分别用GBLUP和ssGBLUP方法计算基因组估计育种值。

    DMU软件是一个全面的集合程序。此软件可用于估计正态分布和非正态分布性状的方差-协方差组分[5]。本研究采用的是AI和EM算法相结合的约束性最大似然(REML)方法估计方差组分。

    方差分析模型为:

    $$ \mathrm{y}=\mathrm{Xb}+{{\mathrm{Z}}_{1}}\mathrm{a}+{{\mathrm{Z}}_{2}}\mathrm{Pe}+\mathrm{e} $$

    式中:y是个体观察值;b是固定效应向量,包括年季效应和胎次效应。a是动物个体加性效应;Pe是永久环境效应;e是残差效应。XZ1Z2分别是baPe的结构矩阵。

    使用DMU软件估计性状间遗传相关性。

    GBLUP模型:与传统的BLUP模型构建原理相似[7],区别在于利用基于SNP信息构建的基因组相关矩阵(G阵)替代常规的基于系谱关系的亲缘关系矩阵(A阵),从而提高GEBV的准确性,其模型如下:

    $$ \begin{align} & \ \ \ \ \ \ \ \ \ \ \ \ \mathrm{y}=\mathrm{I }\!\!\mu\!\!\text{ }+\mathrm{Za}+\mathrm{e}, \\ & \mathrm{a}\tilde{\ }\mathrm{N}(0, \mathrm{G}{{\sigma }^{2}}_{a}), \mathrm{e}\tilde{\ }\mathrm{N}(0, \mathrm{w}{{\sigma }^{2}}_{e}), \\ \end{align} $$

    其中,μ表示反应变量y的平均值;a表示个体的加性遗传效应(即个体育种值);e是残差效应;I为单位矩阵;Za的关联矩阵。G矩阵按照Vanraden提出的方法构建[7];当反应变量为yc时,w=I,本研究通过GVCBLUP软件来利用GBLUP模型。

    一步法GBLUP模型[8]:用H矩阵替代GBLUP中的G矩阵,从而将没有基因型的个体与有基因型的个体放在同一个模型中进行EBV的估计。H矩阵如下:

    $$ \begin{align} & \mathrm{H}=\left[ \begin{matrix} {{G}_{\omega }} & {{G}_{\omega }}A_{11}^{-1}{{A}_{12}} \\ {{A}_{21}}A_{11}^{-1}{{G}_{\omega }} & {{A}_{21}}A_{11}^{-1}{{G}_{\omega }}A_{11}^{-1}{{A}_{12}}+{{A}_{22}}-{{A}_{21}}A_{11}^{-1}{{A}_{12}} \\ \end{matrix} \right]~, \text{ } \\ & \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ {{\mathrm{H}}^{-1}}=\left[ \begin{matrix} G_{\omega }^{-1}-A_{11}^{-1} & 0 \\ 0 & 0 \\ \end{matrix} \right]+{{\mathrm{A}}^{-1}} \\ \end{align} $$

    式中,G为有基因型个体组成的矩阵,A为基于系谱的矩阵。

    根据每个个体GEBV的预测误差的方差(Predictor error variance, PEV),通过下列公式计算出对应的GEBV的理论准确性(Re):

    $$ {{R}_{\text{e}}}=\sqrt{1-{\text{PEV}}/{\sigma _{a}^{2}}\;} $$

    式中,σa2为加性遗传方差。

    初生窝重数据量达到76 710条,平均数为15.76 kg,标准差为4.64 kg,最小值和最大值分别为0.50和40.0 kg,另外根据偏度(-0.18)、峰度(0.54)和Q-Q plot图(图 1),可判断初生窝重基本符合正态分布。

    图  1  初生窝重的Q-Q plot

    初生窝重性状的加性方差、永久环境效应方差分别达到1.414和1.827,残差方差和表型方差分别为14.852和18.093,遗传力为0.08,说明该性状为低遗传力性状,永久环境效应方差占到表型方差的比例为0.10。

    初生窝重与总产仔数、产活仔数和健仔数遗传相关系数分别为0.59、0.68和0.88,为中等偏高的遗传正相关,与弱差猪数遗传相关系数为-0.17,为较低的遗传负相关。

    将出生日期在2016年之后的母猪作为验证样本,共546头母猪。使用传统BLUP、GBLUP和ssGBLUP计算方法,在个体表型缺失的情况下,比较GEBV的准确性,并计算了不同方法下,546头母猪GEBV的秩相关系数。初生窝重的GEBV的准确性在BLUP、GBLUP和ssGBLUP计算方法下分别为0.32、0.36和0.38,相对于BLUP计算方法,GBLUP和ssGBLUP准确性分别提升了11.11%和15.79%。结果表明,ssGBLUP预测初生窝重育种值的准确性最高,ssGBLUP预测的初生窝重估计育种值与BLUP估计育种值秩相关达到0.63,相关性最高。

    本文初生窝重性状记录达76 710条,数据近似服从正态分布,其遗传力估计值均在文献报道范围内[8];此外,遗传相关结果显示,初生窝重与健仔数遗传相关性最高,达到0.88,与相关报道结果较为接近[3]

    国际知名猪育种公司PIC和Norsvin,对出生窝重性状GEBV估计的准确性均进行过评估,其参考群均在1 000头以上,采用ssGBLUP方法的评估准确性为0.26~0.46[10-11]。本研究采用ssGBLUP方法,利用2 344头母猪构成基因组选择参考群,其育种值估计准确性为0.38,处于正常范围。但需要注意的是,基因组选择技术在各育种核心群中应用,其遗传基础、数据采集以及由基因分型方法不同导致标记位点数目和重量的差异,会对估计育种值的准确性和精确性造成较大的影响,实际应用中应具体问题具体分析。

    本研究以出生窝重性状为研究对象,评估了某大白猪核心育种场出生窝重的遗传参数,估计了其与主要繁殖性状的遗传相关性,通过对该性状的选择,能够有效促进性状的遗传改良,尤其是出生健仔数;另外通过构建大白猪基因组选择参考群体,评价了ssGBLUP能够有效提高基因组选择估计育种值的准确性。通过本研究可以发现,基因组选择能够一定程度上提高初生窝重等低遗传力性状的选择准确性,但是如何将此准确性转化为遗传进展,或是提高生产表现,还需要结合和优化实际生产状况,开发更具性价比和准确性的分型方法,或是需要更加灵活、全面和有效的育种方案。总之,本研究为基因组选择的应用奠定了基础,有利于进一步提高繁殖效率。

  • 图  1   抑制剂MG-132和PR-619对SPAE细胞存活率的影响

    *和**分别表示细胞存活率在P<0.05和P<0.01水平显著降低(t检验)。

    Figure  1.   Effect of inhibitors MG-132 and PR-619 on survival rates of SPAE cells

    * and ** indicate that the cell survival rate significantly decreased at P<0.05 and P<0.01 levels respectively (t test).

    图  2   抑制剂MG-132(A~D) 和PR-619(E~H) 对BTV感染SPAE细胞基因转录水平的影响

    *和**分别表示在P<0.05和P<0.01水平差异显著(t检验)。

    Figure  2.   Effects of inhibitors MG-132 (A−D) and PR-619 (E−H) on gene transcriptional levels of BTV-infected SPAE cells

    * and ** indicate significant differences at P<0.05 and P<0.01 levels respectively (t test).

    图  3   利用Western-blotting检测抑制剂处理BTV感染SPAE细胞的蛋白表达水平

    Figure  3.   Detection of protein expression levels in BTV-infected SPAE cells treated with inhibitors by Western blotting

    图  4   抑制剂MG-132(A~D)和PR-169(E~H)对BTV感染SPAE细胞蛋白表达水平的影响

    *和**分别表示在P<0.05和P<0.01水平差异显著(t检验)。

    Figure  4.   Effects of inhibitors MG-132 (A−D) and PR-169 (E−H) on protein expression levels of BTV-infected SPAE cells

    * and ** indicate significant differences at P<0.05 and P<0.01 levels respectively (t test)

    图  5   利用免疫荧光检测抑制剂处理BTV感染SPAE细胞的IRF3核转移水平

    Figure  5.   Detection of IRF3 nuclear translocation level in BTV-infected SPAE cells treated with inhibitors by immunofluorescence

    图  6   抑制剂处理BTV感染SPAE细胞IRF3核转移水平的变化

    *和**分别表示在P<0.05和P<0.01水平差异显著(t检验)。

    Figure  6.   Changes of nuclear translocation ratio of IRF3 in BTV-infected SPAE cells treated with inhibitors

    * and ** indicate significant differences at P<0.05 and P<0.01 levels respectively (t test).

    图  7   抑制剂处理BTV感染SPAE细胞IFN-α基因转录水平(A、C)和IFN-α蛋白表达水平(B、D)变化

    *和**分别表示在P<0.05和P<0.01水平差异显著(t检验)。

    Figure  7.   Changes in IFN-α gene transcriptional levels (A, C) and IFN-α protein expression levels (B, D) in BTV-infected SPAE cells treated with inhibitors

    * and ** indicate significant differences at P<0.05 and P<0.01 levels respectively (t test)

    图  8   抑制剂处理BTV感染SPAE细胞BTV基因组拷贝数变化

    *和**分别表示在P<0.05和P<0.01水平差异显著(t检验)。

    Figure  8.   Changes in BTV genome copy numbers of BTV-infected SPAE cells treated with inhibitors

    * and ** indicate significant differences at P<0.05 and P<0.01 levels respectively (t test)

    表  1   RT-qPCR使用的引物和探针

    Table  1   The primers and probe used for RT-qPCR

    基因名称
    Gene name
    正向引物序列(5'→3')
    Forward primer sequence
    反向引物序列(5'→3')
    Reverse primer sequence
    参考文献或序列
    Reference or sequence
    RIG-I GCCTTAAAGAACTGGATTGA ATACCCATTGTCTGATTTGTT [20]
    USP4 CGACATAAATTCCCTTGCCAC CGTGCTTCTCATACGTCTCAG XM_004018463
    RNF125 TGCCGTTCTTGCATCGCTA CACCTTGCTGTTGTCTCTCCA XM_027960741
    IRF3 GAGGACCACAGCAAGGACTC TGTCTGCCATTGTCTTGAGC [21]
    IFN-α GCACTGGATCAGCAGCTCACTG CTCAAGACTTCTGCTCTGACAACCT [22]
    18S GATCCATTGGAGGGCAAGTCT GCAGCAACTTTAATATACGCTATTGG [23]
    下载: 导出CSV
  • [1]

    ALKHAMIS M A, AGUILAR-VEGA C, FOUNTAIN-JONES N M, et al. Global emergence and evolutionary dynamics of bluetongue virus[J]. Scientific Reports, 2020, 10: 21677. doi: 10.1038/s41598-020-78673-9.

    [2]

    GONG Q L, WANG Q, YANG X Y, et al. Seroprevalence and risk factors of the bluetongue virus in cattle in China from 1988 to 2019: A comprehensive literature review and meta-analysis[J]. Frontiers in Veterinary Science, 2021, 7: 550381. doi: 10.3389/fvets.2020.550381.

    [3]

    MCLAUGHLIN B E, DEMAULA C D, WILSON W C, et al. Replication of bluetongue virus and epizootic hemorrhagic disease virus in pulmonary artery endothelial cells obtained from cattle, sheep, and deer[J]. American Journal of Veterinary Research, 2003, 64(7): 860-865. doi: 10.2460/ajvr.2003.64.860

    [4]

    DEMAULA C D, JUTILA M A, WILSON D W, et al. Infection kinetics, prostacyclin release and cytokine-mediated modulation of the mechanism of cell death during bluetongue virus infection of cultured ovine and bovine pulmonary artery and lung microvascular endothelial cells[J]. Journal of General Virology, 2001, 82(Pt 4): 787-794.

    [5]

    NIEDBALSKI W. Bluetongue virus in Europe: The current epidemiological situation[J]. Medycyna Weterynaryjna, 2022, 78(3). doi: 10.21521/mw.6619.

    [6]

    GOLENDER N, ELDAR A, EHRLICH M, et al. Genomic analysis illustrated a single introduction and evolution of Israeli bluetongue serotype 8 virus population 2008−2019[J]. Microorganisms, 2021, 9(9): 1955. doi: 10.3390/microorganisms9091955.

    [7]

    RATINIER M, CAPORALE M, GOLDER M, et al. Identification and characterization of a novel non-structural protein of bluetongue virus[J]. PLoS Pathogens, 2011, 7(12): e1002477. doi: 10.1371/journal.ppat.1002477

    [8]

    ARIMOTO K, TAKAHASHI H, HISHIKI T, et al. Negative regulation of the RIG-I signaling by the ubiquitin ligase RNF125[J]. Proceedings of the National Academy of Sciences of the United States of America, 2007, 104(18): 7500-7505.

    [9]

    THORESEN D, WANG W, GALLS D, et al. The molecular mechanism of RIG-I activation and signaling[J]. Immunological Reviews, 2021, 304(1): 154-168. doi: 10.1111/imr.13022

    [10]

    ROJAS J M, AVIA M, MARTÍN V, et al. Inhibition of the IFN response by bluetongue virus: The story so far[J]. Frontiers in Microbiology, 2021, 12: 692069. doi: 10.3389/fmicb.2021.692069.

    [11]

    SWATEK K N, KOMANDER D. Ubiquitin modifications[J]. Cell Research, 2016, 26(4): 399-422. doi: 10.1038/cr.2016.39

    [12]

    WANG L, ZHAO W, ZHANG M, et al. USP4 positively regulates RIG-I-mediated antiviral response through deubiquitination and stabilization of RIG-I[J]. Journal of Virology, 2013, 87(8): 4507-4515. doi: 10.1128/JVI.00031-13

    [13]

    XU C, PENG Y, ZHANG Q, et al. USP4 positively regulates RLR-induced NF-κB activation by targeting TRAF6 for K48-linked deubiquitination and inhibits enterovirus 71 replication[J]. Scientific Reports, 2018, 8: 13418. doi: 10.1038/s41598-018-31734-6.

    [14]

    DU J, XING S, TIAN Z, et al. Proteomic analysis of sheep primary testicular cells infected with bluetongue virus[J]. PROTEOMICS, 2016, 16(10): 1499-1514. doi: 10.1002/pmic.201500275

    [15]

    LU D F, LI Z Y, ZHU P, et al. Whole-transcriptome analyses of sheep embryonic testicular cells infected with the bluetongue virus[J]. Frontiers in Immunology, 2022, 13: 1053059. doi: 10.3389/fimmu.2022.1053059.

    [16]

    ZHU J, YANG H, LI H, et al. Full-genome sequence of bluetongue virus serotype 1 (BTV-1) strain Y863, the first BTV-1 isolate of eastern origin found in China[J]. Genome Announcements, 2013, 1(4): e00403-13.

    [17]

    RAMAKRISHNAN M A. Determination of 50% endpoint titer using a simple formula[J]. World Journal of Virology, 2016, 5(2): 85-86. doi: 10.5501/wjv.v5.i2.85

    [18]

    LI W T, JIN X, SONG S J, et al. Blocking SLC7A11 attenuates the proliferation of esophageal squamous cell carcinoma cells[J]. Animal Cells and Systems, 2024, 28(1): 237-250. doi: 10.1080/19768354.2024.2346981

    [19]

    LIVAK K J, SCHMITTGEN T D. Analysis of relative gene expression data using real-time quantitative PCR and the 2‒ΔΔCt method[J]. Methods, 2001, 25(4): 402-408. doi: 10.1006/meth.2001.1262

    [20]

    SASSU E L, KANGETHE R T, SETTYPALLI T B K, et al. Development and evaluation of a real-time PCR panel for the detection of 20 immune markers in cattle and sheep[J]. Veterinary Immunology and Immunopathology, 2020, 227: 110092. doi: 10.1016/j.vetimm.2020.

    [21]

    WANI S A, SAHU A R, SAXENA S, et al. Expression kinetics of ISG15, IRF3, IFNγ, IL10, IL2 and IL4 genes vis-a-vis virus shedding, tissue tropism and antibody dynamics in PPRV vaccinated, challenged, infected sheep and goats[J]. Microbial Pathogenesis, 2018, 117: 206-218. doi: 10.1016/j.micpath.2018.02.027

    [22]

    LI H, CUNHA C W, DAVIES C J, et al. Ovine herpesvirus 2 replicates initially in the lung of experimentally infected sheep[J]. Journal of General Virology, 2008, 89(Pt 7): 1699-1708.

    [23]

    ZARATE M A, WESOLOWSKI S R, NGUYEN L M, et al. In utero inflammatory challenge induces an early activation of the hepatic innate immune response in late gestation fetal sheep[J]. Innate Immunity, 2020, 26(7): 549-564. doi: 10.1177/1753425920928388

    [24] 杨振兴, 朱建波, 李占鸿, 等. 蓝舌病病毒和流行性出血病病毒双重荧光定量RT-PCR检测方法的建立及应用[J]. 中国兽医科学, 2019, 49(9): 1104-1111.
    [25]

    CHIANG C, LIU G, GACK M U. Viral evasion of RIG-I-like receptor-mediated immunity through dysregulation of ubiquitination and ISGylation[J]. Viruses, 2021, 13(2): 182. doi: 10.3390/v13020182.

    [26]

    HUANG S, CHENG A, WANG M, et al. Viruses utilize ubiquitination systems to escape TLR/RLR-mediated innate immunity[J]. Frontiers in Immunology, 2022, 13: 1065211. doi: 10.3389/fimmu.2022.1065211.

    [27]

    LUTZ L M, PACE C R, ARNOLD M M. Rotavirus NSP1 associates with components of the cullin RING ligase family of E3 ubiquitin ligases[J]. Journal of Virology, 2016, 90(13): 6036-6048. doi: 10.1128/JVI.00704-16

    [28]

    LÓPEZ T, SILVA-AYALA D, LÓPEZ S, et al. Replication of the rotavirus genome requires an active ubiquitin-proteasome system[J]. Journal of Virology, 2011, 85(22): 11964-11971. doi: 10.1128/JVI.05286-11

    [29]

    LIU X, CUI L, TAO Y, et al. The deubiquitinase BAP1 and E3 ligase UBE3C sequentially target IRF3 to activate and resolve the antiviral innate immune response[J]. Cell Reports, 2024, 43(8): 114608. doi: 10.1016/j.celrep.2024.114608.

    [30]

    KUANG P P, GOLDSTEIN R H. Regulation of elastin gene transcription by proteasome dysfunction[J]. American Journal of Physiology-Cell Physiology, 2005, 289(3): C766-C773. doi: 10.1152/ajpcell.00525.2004

    [31]

    WANG Y, SUN W, DU B, et al. Therapeutic effect of MG-132 on diabetic cardiomyopathy is associated with its suppression of proteasomal activities: Roles of Nrf2 and NF-κB[J]. American Journal of Physiology-Heart and Circulatory Physiology, 2013, 304(4): H567-H578. doi: 10.1152/ajpheart.00650.2012

图(8)  /  表(1)
计量
  • 文章访问数:  24
  • HTML全文浏览量:  3
  • PDF下载量:  15
  • 被引次数: 0

目录

/

返回文章
返回