Transcriptome profiling highlights regulated biological processes and type III interferon antiviral responses upon Crimean-Congo hemorrhagic fever virus infection

Qiong Mo; Kuan Feng; Shiyu Dai; Qiaoli Wu; Zhong Zhang; Ashaq Ali; Fei Deng; Hualin Wang; Yun-Jia Ning

doi:10.1016/j.virs.2022.09.002

February 2023

. doi: 10.1016/j.virs.2022.09.002

Citation: Qiong Mo, Kuan Feng, Shiyu Dai, Qiaoli Wu, Zhong Zhang, Ashaq Ali, Fei Deng, Hualin Wang, Yun-Jia Ning. Transcriptome profiling highlights regulated biological processes and type III interferon antiviral responses upon Crimean-Congo hemorrhagic fever virus infection .VIROLOGICA SINICA, 2023, 38(1) : 34-46. http://dx.doi.org/10.1016/j.virs.2022.09.002

转录组分析显示克里米亚刚果出血热病毒调控的关键细胞过程及III型干扰素的抗病毒作用

莫琼 ^a,c ,
冯宽 ^a ,
戴诗雨 ^a,c ,
吴巧丽 ^a ,
张忠 ^a ,
Ashaq Ali ^c,d ,
邓菲 ^a,b,, ,
王华林 ^a,b,, ,
宁云佳 ^a,b,,

a 病毒学国家重点实验室和国家病毒资源中心中国科学院武汉病毒研究所中国武汉;
b 中国科学院生物安全大科学研究中心中国武汉;
c 中国科学院大学中国武汉;
d 科学与应用技术卓越中心巴基斯坦伊斯兰堡

通讯作者： 邓菲, df@wh.iov.cn; 王华林, h.wang@wh.iov.cn; 宁云佳, nyj@wh.iov.cn
收稿日期： 2022-05-10
录用日期： 2022-08-12

摘要

克里米亚刚果出血热病毒（Crimean-Congo hemorrhagic fever virus，CCHFV）属于生物安全四级（biosafety level-4，BSL-4）病毒，其感染会引起以出血热症状、多器官功能衰竭及高死亡率为特点的克里米亚刚果出血热（Crimean-Congo hemorrhagic fever，CCHF），该病毒对人类公共健康造成了极大的威胁。近年来有关CCHFV研究的报道逐渐增多，但其感染调控的宿主响应的特征还有待进一步探索。为全面深入了解CCHFV感染对宿主的影响，本研究利用高通量RNA测序技术（high-throughput RNA sequencing，RNA-seq）对CCHFV感染人肾细胞（293）的转录组学进行了分析。结果表明，在293细胞中，CCHFV的感染可导致496个基因的差异表达，其中上调表达基因361个，下调表达基因135个。进一步生物信息学分析发现，差异表达基因所涉及的生物学进程主要包括宿主防御响应，应激响应，病毒调节，免疫反应，代谢、应激、凋亡及蛋白分解等相关过程，其中以III型干扰素信号通路相关基因及内质网（ER）应激响应相关的基因上调最为显著。RT-qPCR验证试验得到了与RNA-seq相似的结果，强烈暗示III型干扰素响应等过程在病毒感染中可能具有关键调控作用。而且功能试验分析发现III型干扰素即便在低浓度作用时亦具有明显的抗CCHFV复制活性。本研究结果为全面了解CCHFV与宿主的相互作用提供了新的基础与依据，可能对CCHFV的预防和治疗工作具有指导意义。
- 克里米亚刚果出血热病毒(CCHFV)
- , 生物安全四级病原
- , 布尼亚病毒
- , 转录组
- , III型干扰素
- , 内质网应激
- , 病毒-宿主互作
- , 抗病毒治疗

Transcriptome profiling highlights regulated biological processes and type III interferon antiviral responses upon Crimean-Congo hemorrhagic fever virus infection

Qiong Mo ^a,c ,
Kuan Feng ^a ,
Shiyu Dai ^a,c ,
Qiaoli Wu ^a ,
Zhong Zhang ^a ,
Ashaq Ali ^c,d ,
Fei Deng ^a,b,, ,
Hualin Wang ^a,b,, ,
Yun-Jia Ning ^a,b,,

a. State Key Laboratory of Virology and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071/430207, China;
b. Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071/430207, China;
c. University of Chinese Academy of Sciences, Beijing, 101408, China;
d. Centre of Excellence in Science and Applied Technologies, Islamabad, 45320, Pakistan

Corresponding author: Fei Deng, df@wh.iov.cn Hualin Wang, h.wang@wh.iov.cn Yun-Jia Ning, nyj@wh.iov.cn
Received Date: 10 May 2022
Accepted Date: 12 August 2022

Abstract

Crimean-Congo hemorrhagic fever virus (CCHFV) is a biosafety level-4 (BSL-4) pathogen that causes Crimean-Congo hemorrhagic fever (CCHF) characterized by hemorrhagic manifestation, multiple organ failure and high mortality rate, posing great threat to public health. Despite the recently increasing research efforts on CCHFV, host cell responses associated with CCHFV infection remain to be further characterized. Here, to better understand the cellular response to CCHFV infection, we performed a transcriptomic analysis in human kidney HEK293 cells by high-throughput RNA sequencing (RNA-seq) technology. In total, 496 differentially expressed genes (DEGs), including 361 up-regulated and 135 down-regulated genes, were identified in CCHFV-infected cells. These regulated genes were mainly involved in host processes including defense response to virus, response to stress, regulation of viral process, immune response, metabolism, stimulus, apoptosis and protein catabolic process. Therein, a significant up-regulation of type III interferon (IFN) signaling pathway as well as endoplasmic reticulum (ER) stress response was especially remarkable. Subsequently, representative DEGs from these processes were well validated by RT-qPCR, confirming the RNA-seq results and the typical regulation of IFN responses and ER stress by CCHFV. Furthermore, we demonstrate that not only type I but also type III IFNs (even at low dosages) have substantial anti-CCHFV activities. Collectively, the data may provide new and comprehensive insights into the virus-host interactions and particularly highlights the potential role of type III IFNs in restricting CCHFV, which may help inform further mechanistic delineation of the viral infection and development of anti-CCHFV strategies.
- Crimean-Congo hemorrhagic fever virus (CCHFV)
- , Biosafety level-4 (BSL-4) pathogen
- , Bunyavirus
- , Transcriptome
- , Type III interferon
- , ER stress
- , Virus-host interaction
- , Antiviral therapeutics

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