Division of Veterinary Biotechnology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, 243122, India; School of Informatics and Computing, Indiana University Purdue University, 719 Indiana Ave Ste 319, Walker Plaza Building, Indianapolis, IN 46202, United States.
Division of Veterinary Biotechnology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, 243122, India.
Virus Res. 2017 Feb 2;229:28-40. doi: 10.1016/j.virusres.2016.12.014. Epub 2016 Dec 23.
Peste des petits ruminanats virus (PPRV), a morbillivirus causes an acute, highly contagious disease - peste des petits ruminants (PPR), affecting goats and sheep. Sungri/96 vaccine strain is widely used for mass vaccination programs in India against PPR and is considered the most potent vaccine providing long-term immunity. However, occurrence of outbreaks due to emerging PPR viruses may be a challenge. In this study, the temporal dynamics of immune response in goat peripheral blood mononuclear cells (PBMCs) infected with Sungri/96 vaccine virus was investigated by transcriptome analysis. Infected goat PBMCs at 48h and 120h post infection revealed 2540 and 2000 differentially expressed genes (DEGs), respectively, on comparison with respective controls. Comparison of the infected samples revealed 1416 DEGs to be altered across time points. Functional analysis of DEGs reflected enrichment of TLR signaling pathways, innate immune response, inflammatory response, positive regulation of signal transduction and cytokine production. The upregulation of innate immune genes during early phase (between 2-5 days) viz. interferon regulatory factors (IRFs), tripartite motifs (TRIM) and several interferon stimulated genes (ISGs) in infected PBMCs and interactome analysis indicated induction of broad-spectrum anti-viral state. Several Transcription factors - IRF3, FOXO3 and SP1 that govern immune regulatory pathways were identified to co-regulate the DEGs. The results from this study, highlighted the involvement of both innate and adaptive immune systems with the enrichment of complement cascade observed at 120h p.i., suggestive of a link between innate and adaptive immune response. Based on the transcriptome analysis and qRT-PCR validation, an in vitro mechanism for the induction of ISGs by IRFs in an interferon independent manner to trigger a robust immune response was predicted in PPRV infection.
小反刍兽疫病毒（PPRV）是一种麻疹病毒，可引起急性、高度传染性疾病——小反刍兽疫（PPR），影响山羊和绵羊。Sungri/96 疫苗株广泛用于印度针对 PPR 的大规模疫苗接种计划，被认为是提供长期免疫力的最有效疫苗。然而，新兴 PPR 病毒的爆发可能是一个挑战。在这项研究中，通过转录组分析研究了感染 Sungri/96 疫苗病毒的山羊外周血单核细胞（PBMC）中的免疫反应的时间动态。与各自的对照相比，感染后 48h 和 120h 的山羊 PBMC 分别显示出 2540 和 2000 个差异表达基因（DEG）。对感染样本的比较显示，1416 个 DEG 在不同时间点发生变化。DEG 的功能分析反映了 TLR 信号通路、固有免疫反应、炎症反应、信号转导的正调节和细胞因子产生的富集。感染 PBMC 中早期（2-5 天）固有免疫基因的上调，干扰素调节因子（IRFs）、三部分基序（TRIM）和几种干扰素刺激基因（ISGs），以及相互作用分析表明诱导了广谱抗病毒状态。鉴定出几个转录因子 - IRF3、FOXO3 和 SP1，它们控制免疫调节途径，共同调节 DEGs。这项研究的结果强调了固有免疫和适应性免疫系统的参与，在感染后 120h 观察到补体级联的富集，表明固有免疫和适应性免疫反应之间存在联系。基于转录组分析和 qRT-PCR 验证，预测了在 PPRV 感染中 IRF 以干扰素非依赖的方式诱导 ISGs 的体外机制，以触发强大的免疫反应。
