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鸭胚成纤维细胞对鸭坦布苏病毒感染的动态反应及凋亡基因双重调控的转录组分析

Transcriptome analysis of duck embryo fibroblasts for the dynamic response to duck tembusu virus infection and dual regulation of apoptosis genes.

作者信息

Pan Yuhong, Cheng Anchun, Zhang Xingcui, Wang Mingshu, Chen Shun, Zhu Dekang, Liu Mafeng, Zhao Xinxin, Yang Qiao, Wu Ying, Huang Juan, Zhang Shaqiu, Mao Sai, Ou Xumin, Gao Qun, Yu Yanling, Liu Yunya, Zhang Ling, Yin Zhongqiong, Jing Bo, Tian Bin, Pan Leichang, Rehman Mujeeb Ur, Chen Xiaoyue, Jia Renyong

机构信息

Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China.

Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, Sichuan, China.

出版信息

Aging (Albany NY). 2020 Sep 7;12(17):17503-17527. doi: 10.18632/aging.103759.

Abstract

Duck Tembusu virus (DTMUV) is an emerging pathogenic flavivirus that has caused enormous economic losses in Southeast Asia. However, the pathogenic mechanism and host's responses after DTMUV infection remain poorly understood. During this study, total mRNA sequencing (RNA-Seq) analysis was used to detect the global gene expression in DEFs at various time points after DTMUV infection. We identified 326 genes altered significantly at all time points, and these genes were dynamically enriched in multifarious biological processes, including apoptosis, innate immune response, DNA replication, cell cycle arrest and DNA repair. Next, the results showed that apoptosis was induced and the proportion of apoptosis increased with time, and pro-apoptotic molecules caspases were activated. The RNA-seq data analysis further revealed that most pro-apoptosis and anti-apoptosis genes were early continually responsive, and the genes involved in both intrinsic and extrinsic apoptotic pathways were initiated. Further, the considerably enriched immune-relevant pathways were involved in apoptosis process, and protein-protein interactions (PPIs) analysis showed that IL6, STAT1, TNFAIP3, CFLAR and PTGS2 may be key regulators of DEFs apoptosis. In conclusion, this study not only contributes to understanding the underlying mechanism of DEFs infection with DTMUV, but also provides new insights into targets screening for antiviral therapy.

摘要

鸭坦布苏病毒(DTMUV)是一种新出现的致病性黄病毒,已在东南亚地区造成巨大经济损失。然而,DTMUV感染后的致病机制和宿主反应仍知之甚少。在本研究中,采用全mRNA测序(RNA-Seq)分析来检测DTMUV感染后不同时间点鸭胚成纤维细胞(DEFs)中的整体基因表达。我们鉴定出在所有时间点均显著改变的326个基因,这些基因在多种生物学过程中动态富集,包括细胞凋亡、固有免疫反应、DNA复制、细胞周期阻滞和DNA修复。接下来,结果显示诱导了细胞凋亡,且凋亡比例随时间增加,促凋亡分子半胱天冬酶被激活。RNA-seq数据分析进一步表明,大多数促凋亡和抗凋亡基因早期持续反应,且参与内源性和外源性凋亡途径的基因均被启动。此外,显著富集的免疫相关途径参与了凋亡过程,蛋白质-蛋白质相互作用(PPI)分析表明,IL6、STAT1、TNFAIP3、CFLAR和PTGS2可能是DEFs凋亡的关键调节因子。总之,本研究不仅有助于理解DEFs感染DTMUV的潜在机制,还为抗病毒治疗的靶点筛选提供了新见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3b9/7521532/9f2be4cf5623/aging-12-103759-g001.jpg

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