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 under-stand 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 pro-cess.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 pro-cesses were well validated by RT-qPCR,confirming the RNA-seq results and the typical regulation of IFN re-sponses 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.
基金项目
National Key Research and Development Program of China(2018YFA0507202)
National Natural Science Foundation of China(32170171)
National Natural Science Foundation of China(31870162)
National Natural Science Foundation of China(82161138003)
Youth Innovation Promotion Association of Chinese Academy of Sciences()
Institutional Center for Shared Technologies and Facilities of Wuhan Institute of Virology()
CAS for technical assistance and the National Virus Resource Center(Wuhan Institute of Virology)for virus resources()
running team of National Biosafety Laboratory,Wuhan,Chinese Academy of Sciences()
国家科技期刊平台
NSTL
万方数据