Transcriptome-wide search for Carpathian goat factors associated with proviral load of small ruminant lentiviruses in goats

Purpose: RNA-sequencing (RNA-seq) was used to identify the changes in gene expression in goats carrying high (HPL) and low (LPL) proviral load of SRLV. For the first time, differentially expressed transcriptome profiles in these two group of animals were identified, and information about genes and mechanisms, and relevant pathways inferred via bioinformatics analyses. The results provided unique insights for further exploring and understanding the host responses to SRLV infection in goats. Results: Data enabled to identify 1434 significant differentially expressed genes between HPL and LPL goats. Of these genes, 571 were upregulated and the remaining 863 genes were downregulated in HPL goats. GO enrichment analysis showed that the identified DEGs were found to have significantly enriched regulation of signaling receptor activity, the response to toxic substance, NADH dehydrogenase complex assembly, cytokine production, vesicle and vacuole organization. In turn, KEGG pathway tool classified DEGs that enrich molecular processes such as B and T cell receptor signaling pathways, natural killer cell-mediated cytotoxicity, Fc gamma R-mediated phagocytosis, toll-like receptor signaling pathways, TNF, mTOR signaling and Foxo signaling pathway, etc. Conclusions: In this descriptive study, our findings revealed the changes in the host transcriptome expression profile between HPL and LPL goats during SRLV infection and suggested that changes in proviral load induced altering the host’s metabolic network and expression of genes related to host immune responses, including inflammation, cell locomotion, cytokine production, defense response etc. The above findings provided unique insights for further studies on the mechanisms underlying SRLV-host interactions. The whole blood transcriptome sequencing was performed for 12 samples collected form Carpathian goats using HiSeq High-Output v4 - SR (Illumina) into 50 single-end cycles.

研究目的：本研究采用RNA测序（RNA-seq）技术，旨在鉴定携带高（HPL）、低（LPL）小反刍兽慢病毒（Small Ruminant Lentivirus, SRLV）病毒载量的山羊体内基因表达的变化情况。本研究首次鉴定了这两组山羊的差异表达转录组谱，并通过生物信息学分析推断出相关基因、调控机制及信号通路信息，研究结果为进一步探索和理解山羊宿主对SRLV感染的应答反应提供了独特的研究视角。

研究结果：本数据集共鉴定出HPL与LPL山羊间存在1434个显著差异表达基因（Differentially Expressed Genes, DEGs），其中571个基因在HPL山羊中呈上调表达，剩余863个基因呈下调表达。基因本体（Gene Ontology, GO）富集分析结果显示，鉴定得到的DEGs显著富集于信号受体活性调控、有毒物质应答、NADH脱氢酶复合物组装、细胞因子生成、囊泡与液泡组织等生物学过程。京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）通路分析则将DEGs归类于多个分子过程相关通路，包括B细胞与T细胞受体信号通路、自然杀伤细胞介导的细胞毒性、FcγR介导的吞噬作用、Toll样受体信号通路、肿瘤坏死因子（Tumor Necrosis Factor, TNF）信号通路、雷帕霉素靶蛋白（mammalian target of rapamycin, mTOR）信号通路以及叉头框O（Forkhead box O, Foxo）信号通路等。

研究结论：本描述性研究揭示了SRLV感染期间HPL与LPL山羊宿主转录组表达谱的差异，表明病毒载量的改变会影响宿主的代谢网络以及与宿主免疫应答相关的基因表达，包括炎症反应、细胞运动、细胞因子生成、防御应答等过程。上述研究结果为进一步探究SRLV与宿主互作的潜在机制提供了全新的研究思路。本研究共收集12份喀尔巴阡山羊全血样本，采用Illumina公司的HiSeq High-Output v4 - SR测序平台进行50个单端循环的全血转录组测序。