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山羊外周血单个核细胞(PBMC)感染小反刍兽疫疫苗病毒(Sungri/96)的早期转录组谱显示,以干扰素非依赖性方式诱导抗病毒反应。

Early transcriptome profile of goat peripheral blood mononuclear cells (PBMCs) infected with peste des petits ruminant's vaccine virus (Sungri/96) revealed induction of antiviral response in an interferon independent manner.

机构信息

Division of Veterinary Biotechnology, ICAR-Indian Veterinary Research Institute, Izatnagar 243122, India; Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, 5021 Health Information and Translational Sciences (HITS), 410 West 10th Street, Indianapolis, IN, 46202, USA.

Division of Veterinary Biotechnology, ICAR-Indian Veterinary Research Institute, Izatnagar 243122, India.

出版信息

Res Vet Sci. 2019 Jun;124:166-177. doi: 10.1016/j.rvsc.2019.03.014. Epub 2019 Mar 14.

Abstract

Sungri/96 vaccine strain is considered the most potent vaccine providing long-term immunity against peste des petits ruminants (PPR) in India. Previous studies in our laboratory highlighted induction of robust antiviral response in an interferon independent manner at 48 h and 120 h post infection (p.i.). However, immune response at the earliest time point 6 h p.i. (time taken to complete one PPRV life cycle), in PBMCs infected with Sungri/96 vaccine virus has not been investigated. This study was taken up to understand the global gene expression profiling of goat PBMCs after Sungri/96 PPRV vaccine strain infection at 6 h post infection (p.i.). A total of 1926 differentially expressed genes (DEGs) were identified with 616 - upregulated and 1310 - downregulated. TLR7/TLR3, IRF7/IRF1, ISG20, IFIT1/IFIT2, IFITM3, IL27 and TREX1 were identified as key immune sensors and antiviral candidate genes. Interestingly, type I interferons (IFNα/β) were not differentially expressed at this time point as well. TREX1, an exonuclease which inhibits type I interferons at the early stage of virus infection was found to be highly upregulated. IL27, an important antiviral host immune factor was significantly upregulated. ISG20, an antiviral interferon induced gene with exonuclease activity specific to ssRNA viruses was highly expressed. Functional profiling of DEGs showed significant enrichment of immune system processes with 233 genes indicating initiation of immune defense response in host cells. Protein interaction network showed important innate immune molecules in the immune network with high connectivity. The study highlights important immune and antiviral genes at the earliest time point.

摘要

Sungri/96 疫苗株被认为是在印度提供针对小反刍兽疫(PPR)长期免疫的最有效疫苗。我们实验室之前的研究强调了在感染后 48 小时和 120 小时以干扰素非依赖性方式诱导强大的抗病毒反应。然而,在感染 Sungri/96 疫苗病毒的 PBMC 中,感染后 6 小时(完成一个 PPRV 生命周期所需的时间)的最早时间点的免疫反应尚未得到研究。本研究旨在了解 Sungri/96 PPRV 疫苗株感染后 6 小时感染 PBMC 的山羊全基因表达谱。在感染后 6 小时(感染后 6 小时)共鉴定出 1926 个差异表达基因(DEGs),其中 616 个上调,1310 个下调。TLR7/TLR3、IRF7/IRF1、ISG20、IFIT1/IFIT2、IFITM3、IL27 和 TREX1 被鉴定为关键的免疫传感器和抗病毒候选基因。有趣的是,在这个时间点也没有检测到 I 型干扰素(IFNα/β)的差异表达。TREX1 是一种在病毒感染的早期抑制 I 型干扰素的核酸外切酶,其表达水平被发现高度上调。IL27,一种重要的抗病毒宿主免疫因子,显著上调。ISG20,一种具有 ssRNA 病毒特异性核酸外切酶活性的抗病毒干扰素诱导基因,高度表达。DEGs 的功能分析显示,免疫系统过程显著富集,有 233 个基因表明宿主细胞中免疫防御反应的启动。蛋白质相互作用网络显示,在免疫网络中具有高连通性的重要先天免疫分子。该研究强调了在最早时间点的重要免疫和抗病毒基因。

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