CHU de Québec Research Center, Department of Microbiology, Infectious Diseases and Immunology, Faculty of Medicine, Université Laval, Quebec, QC G1V 4G2, Canada.
Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3B 3M9, Canada.
Int J Mol Sci. 2021 Apr 6;22(7):3792. doi: 10.3390/ijms22073792.
Ebola virus (EBOV) is a virulent pathogen, notorious for inducing life-threatening hemorrhagic fever, that has been responsible for several outbreaks in Africa and remains a public health threat. Yet, its pathogenesis is still not completely understood. Although there have been numerous studies on host transcriptional response to EBOV, with an emphasis on the clinical features, the impact of EBOV infection on post-transcriptional regulatory elements, such as microRNAs (miRNAs), remains largely unexplored. MiRNAs are involved in inflammation and immunity and are believed to be important modulators of the host response to viral infection. Here, we have used small RNA sequencing (sRNA-Seq), qPCR and functional analyses to obtain the first comparative miRNA transcriptome (miRNome) of a human liver cell line (Huh7) infected with one of the following three EBOV strains: Mayinga (responsible for the first Zaire outbreak in 1976), Makona (responsible for the West Africa outbreak in 2013-2016) and the epizootic Reston (presumably innocuous to humans). Our results highlight specific miRNA-based immunity pathways and substantial differences between the strains beyond their clinical manifestation and pathogenicity. These analyses shed new light into the molecular signature of liver cells upon EBOV infection and reveal new insights into miRNA-based virus attack and host defense strategy.
埃博拉病毒(EBOV)是一种烈性病原体,以引起危及生命的出血热而闻名,曾在非洲引发多次疫情,仍然是公共卫生的威胁。然而,其发病机制仍不完全清楚。尽管已经有许多关于宿主对 EBOV 转录反应的研究,重点是临床特征,但 EBOV 感染对转录后调节元件(如 microRNAs (miRNAs))的影响在很大程度上仍未得到探索。miRNAs 参与炎症和免疫反应,被认为是宿主对病毒感染反应的重要调节剂。在这里,我们使用小 RNA 测序(sRNA-Seq)、qPCR 和功能分析,获得了三种 EBOV 株(Mayinga(导致 1976 年扎伊尔的首次爆发)、Makona(导致 2013-2016 年西非的爆发)和流行的 Reston(推测对人类无害)感染人肝细胞系(Huh7)的首个比较 miRNA 转录组(miRNome)。我们的结果突出了特定的基于 miRNA 的免疫途径,以及除了临床表现和致病性之外,株间的实质性差异。这些分析为 EBOV 感染后肝细胞的分子特征提供了新的认识,并揭示了 miRNA 为基础的病毒攻击和宿主防御策略的新见解。