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Genomic analysis of host – Peste des petits ruminants vaccine viral transcriptome uncovers transcription factors modulating immune regulatory pathways

机译:宿主-小反刍兽疫疫苗病毒转录组的基因组分析揭示了调节免疫调节途径的转录因子

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摘要

Peste des petits ruminants (PPR), is an acute transboundary viral disease of economic importance, affecting goats and sheep. Mass vaccination programs around the world resulted in the decline of PPR outbreaks. Sungri 96 is a live attenuated vaccine, widely used in Northern India against PPR. This vaccine virus, isolated from goat works efficiently both in sheep and goat. Global gene expression changes under PPR vaccine virus infection are not yet well defined. Therefore, in this study we investigated the host-vaccine virus interactions by infecting the peripheral blood mononuclear cells isolated from goat with PPRV (Sungri 96 vaccine virus), to quantify the global changes in the transcriptomic signature by RNA-sequencing. Viral genome of Sungri 96 vaccine virus was assembled from the PPRV infected transcriptome confirming the infection and demonstrating the feasibility of building a complete non-host genome from the blood transcriptome. Comparison of infected transcriptome with control transcriptome revealed 985 differentially expressed genes. Functional analysis showed enrichment of immune regulatory pathways under PPRV infection. Key genes involved in immune system regulation, spliceosomal and apoptotic pathways were identified to be dysregulated. Network analysis revealed that the protein - protein interaction network among differentially expressed genes is significantly disrupted in infected state. Several genes encoding TFs that govern immune regulatory pathways were identified to co-regulate the differentially expressed genes. These data provide insights into the host - PPRV vaccine virus interactome for the first time. Our findings suggested dysregulation of immune regulatory pathways and genes encoding Transcription Factors (TFs) that govern these pathways in response to viral infection.Electronic supplementary materialThe online version of this article (doi:10.1186/s13567-015-0153-8) contains supplementary material, which is available to authorized users.
机译:小反刍兽疫(PPR)是一种具有重要经济意义的急性跨界病毒病,影响山羊和绵羊。世界各地的大规模疫苗接种计划导致了PPR爆发的减少。 Sungri 96是减毒活疫苗,在印度北部广泛用于抗PPR。从山羊分离出的这种疫苗病毒在绵羊和山羊中均有效。在PPR疫苗病毒感染下的总体基因表达变化尚未明确定义。因此,在这项研究中,我们通过用PPRV(Sungri 96疫苗病毒)感染从山羊分离的外周血单个核细胞来研究宿主-疫苗病毒之间的相互作用,以通过RNA测序来量化转录组特征的总体变化。由PPRV感染的转录组组装了Sungri 96疫苗病毒的病毒基因组,证实了感染,并证明了从血液转录组构建完整的非宿主基因组的可行性。感染的转录组与对照转录组的比较显示了985个差异表达的基因。功能分析显示PPRV感染下的免疫调节途径丰富。涉及免疫系统调节,剪接体和凋亡途径的关键基因被鉴定为失调。网络分析表明,差异表达基因之间的蛋白质-蛋白质相互作用网络在感染状态下被显着破坏。几个编码控制免疫调节途径的TFs的基因被确定来共同调节差异表达的基因。这些数据首次为宿主-PPRV疫苗病毒相互作用组提供了见解。我们的发现表明免疫调节途径和编码转录因子(TFs)的基因表达异常,这些因子可响应病毒感染控制这些途径。电子补充材料本文的在线版本(doi:10.1186 / s13567-015-0153-8)包含补充材料,可供授权用户使用。

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