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

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

  • 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.

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

      Corresponding author: Fei Deng, df@wh.iov.cn
      Corresponding author: Hualin Wang, h.wang@wh.iov.cn
      Corresponding author: Yun-Jia Ning, nyj@wh.iov.cn
    • 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

    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.

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