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

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

机构地区：[1]State Key Laboratory of Virology and National Virus Resource Center,Wuhan Institute of Virology,Chinese Academy of Sciences,Wuhan,430071/430207,China [2]Center for Biosafety Mega-Science,Chinese Academy of Sciences,Wuhan,430071/430207,China [3]University of Chinese Academy of Sciences,Beijing,101408,China [4]Centre of Excellence in Science and Applied Technologies,Islamabad,45320,Pakistan

出　　处：《Virologica Sinica》2023年第1期34-46,共13页中国病毒学（英文版）

基　　金：supported by the National Key Research and Development Program of China(2018YFA0507202);the National Natural Science Foundation of China(32170171,31870162,and 82161138003);the Youth Innovation Promotion Association of Chinese Academy of Sciences.

摘　　要：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.

关 键 词：Crimean-Congo hemorrhagic fever virus(CCHFV) Biosafety level-4(BSL-4)pathogen BUNYAVIRUS Transcriptome Type III interferon ER stress Virus-host interaction Antiviral therapeutics 

分 类 号：S852.4[农业科学—基础兽医学]