University of Lyon, INSA-Lyon, INRA BF2l, Villeurbanne, France.
NVIDIA Corporation, Santa Clara, CA, USA.
Commun Biol. 2021 May 17;4(1):590. doi: 10.1038/s42003-021-02095-0.
The novel betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a worldwide pandemic (COVID-19) after emerging in Wuhan, China. Here we analyzed public host and viral RNA sequencing data to better understand how SARS-CoV-2 interacts with human respiratory cells. We identified genes, isoforms and transposable element families that are specifically altered in SARS-CoV-2-infected respiratory cells. Well-known immunoregulatory genes including CSF2, IL32, IL-6 and SERPINA3 were differentially expressed, while immunoregulatory transposable element families were upregulated. We predicted conserved interactions between the SARS-CoV-2 genome and human RNA-binding proteins such as the heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) and eukaryotic initiation factor 4 (eIF4b). We also identified a viral sequence variant with a statistically significant skew associated with age of infection, that may contribute to intracellular host-pathogen interactions. These findings can help identify host mechanisms that can be targeted by prophylactics and/or therapeutics to reduce the severity of COVID-19.
新型贝塔冠状病毒严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）在中国武汉出现后引发了全球性大流行（COVID-19）。在这里，我们分析了公共宿主和病毒 RNA 测序数据，以更好地了解 SARS-CoV-2 如何与人类呼吸道细胞相互作用。我们鉴定了在 SARS-CoV-2 感染的呼吸道细胞中特异性改变的基因、异构体和转座元件家族。包括 CSF2、IL32、IL-6 和 SERPINA3 在内的众所周知的免疫调节基因表达水平不同，而免疫调节转座元件家族则上调。我们预测了 SARS-CoV-2 基因组与人类 RNA 结合蛋白（如异质核核糖核蛋白 A1（hnRNPA1）和真核起始因子 4（eIF4b）之间的保守相互作用。我们还发现了一种与感染年龄相关的具有统计学意义的病毒序列变异体，它可能与细胞内的宿主-病原体相互作用有关。这些发现有助于确定宿主机制，这些机制可以作为预防和/或治疗的靶点，以降低 COVID-19 的严重程度。
