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小反刍兽疫病毒感染的绵羊和山羊肺与脾中宿主微小RNA转录组的调控

Modulation of Host miRNAs Transcriptome in Lung and Spleen of Peste des Petits Ruminants Virus Infected Sheep and Goats.

作者信息

Pandey Aruna, Sahu Amit R, Wani Sajad A, Saxena Shikha, Kanchan Sonam, Sah Vaishali, Rajak Kaushal K, Khanduri Alok, Sahoo Aditya P, Tiwari Ashok K, Mishra Bina, Muthuchelvan D, Mishra Bishnu P, Singh Raj K, Gandham Ravi K

机构信息

Computational Biology and Genomics Facility Lab, Division of Veterinary Biotechnology, Indian Council of Agricultural Research-Indian Veterinary Research Institute, BareillyIndia.

Division of Biological Products, Indian Council of Agricultural Research-Indian Veterinary Research Institute, BareillyIndia.

出版信息

Front Microbiol. 2017 Jun 26;8:1146. doi: 10.3389/fmicb.2017.01146. eCollection 2017.

Abstract

Peste des petits ruminants (PPR) is one of the highly contagious viral disease, characterized by fever, sore mouth, conjunctivitis, gastroenteritis, and pneumonia, primarily affecting sheep and goats. Reports suggested variable host response in goats and sheep and this host response vis-a-vis the expression of microRNAs (miRNAs) has not been investigated. Here, miRNAs were sequenced and proteomics data were generated to identify the role of differentially expressed miRNA (DEmiRNA) in PPR virus (PPRV) infected lung and spleen tissues of sheep and goats. In lungs, 67 and 37 DEmiRNAs have been identified in goats and sheep, respectively. Similarly, in spleen, 50 and 56 DEmiRNAs were identified in goats and sheep, respectively. A total of 20 and 11 miRNAs were found to be common differentially expressed in both the species in PPRV infected spleen and lung, respectively. Six DEmiRNAs-miR-21-3p, miR-1246, miR-27a-5p, miR-760-3p, miR-320a, and miR-363 were selected based on their role in viral infections, apoptosis, and fold change. The target prediction analysis of these six selected DEmiRNAs from the proteome data generated, revealed involvement of more number of genes in lung and spleen of goats than in sheep. On gene ontology analysis of host target genes these DEmiRNAs were found to regulate several immune response signaling pathways. It was observed that the pathways viz. T cell receptor signaling, Rap1 signaling, Toll-like receptor signaling, and B cell receptor signaling governed by DEmiRNAs were more perturbed in goats than in sheep. The data suggests that PPRV-induced miR-21-3p, miR-320a, and miR-363 might act cooperatively to enhance viral pathogenesis in the lung and spleen of sheep by downregulating several immune response genes. The study gives an important insight into the molecular pathogenesis of PPR by identifying that the PPRV-Izatnagar/94 isolate elicits a strong host response in goats than in sheep.

摘要

小反刍兽疫(PPR)是一种高度传染性的病毒性疾病,其特征为发热、口腔溃疡、结膜炎、肠胃炎和肺炎,主要感染绵羊和山羊。报告显示山羊和绵羊的宿主反应存在差异,而这种宿主反应与微小RNA(miRNA)的表达之间的关系尚未得到研究。在此,对miRNA进行了测序,并生成了蛋白质组学数据,以确定差异表达的miRNA(DEmiRNA)在感染小反刍兽疫病毒(PPRV)的绵羊和山羊肺组织及脾脏组织中的作用。在肺组织中,分别在山羊和绵羊中鉴定出67个和37个DEmiRNA。同样,在脾脏中,分别在山羊和绵羊中鉴定出50个和56个DEmiRNA。在感染PPRV的脾脏和肺组织中,分别共有20个和11个miRNA在两个物种中均差异表达。基于其在病毒感染、细胞凋亡和倍数变化方面的作用,选择了6个DEmiRNA——miR-21-3p、miR-1246、miR-27a-5p、miR-760-3p、miR-320a和miR-363。从生成的蛋白质组数据对这6个选定的DEmiRNA进行靶标预测分析,结果显示,与绵羊相比,在山羊的肺和脾脏中有更多基因参与其中。对宿主靶基因进行基因本体分析发现,这些DEmiRNA可调节多种免疫反应信号通路。据观察,由DEmiRNA调控的T细胞受体信号通路、Rap1信号通路、Toll样受体信号通路和B细胞受体信号通路在山羊中比在绵羊中受到的干扰更大。数据表明,PPRV诱导的miR-21-3p、miR-320a和miR-363可能通过下调多个免疫反应基因而协同作用,增强绵羊肺和脾脏中的病毒致病性。该研究通过确定PPRV-Izatnagar/94毒株在山羊中比在绵羊中引发更强的宿主反应,为PPR的分子发病机制提供了重要见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b11/5483481/5bf090cb3d3e/fmicb-08-01146-g001.jpg

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