核糖体分析显示SARS-CoV-2感染期间抗病毒细胞因子和转录因子的转录后表达受限,bioRxiv - Microbiology

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核糖体分析显示SARS-CoV-2感染期间抗病毒细胞因子和转录因子的转录后表达受限
bioRxiv - Microbiology Pub Date : 2021-03-04 , DOI: 10.1101/2021.03.03.433675
Marina R. Alexander , Aaron M. Brice , Petrus Jansen van Vuren , Christina L. Rootes , Leon Tribolet , Christopher Cowled , Andrew G. D. Bean , Cameron R. Stewart

由SARS-CoV-2引起的全球COVID-19大流行已导致超过220万人死亡。到目前为止，疾病的后果从无症状到严重，对病毒的基因型变化很小，因此了解宿主反应至关重要。转录组学在理解宿主与病原体的相互作用中已变得异常重要。然而，转录后调控通过翻译和mRNA稳定性在感染和免疫中起着重要作用，从而可以严格控制宿主和入侵病毒对有效宿主的反应。在这里，我们应用核糖体分析来评估人类肺上皮细胞系（Calu-3）的SARS-CoV-2感染过程中宿主基因的转录后调控。我们已经确定了许多转录因子（JUN，ZBTB20，ATF3，HIVEP2和EGR1）以及精选的抗病毒细胞因子基因，IFNB1，IFNL1,2和3，IL-6和CCL5在转录后水平受到SARS-CoV-2感染的限制，并讨论了其对宿主对感染反应的影响。肺中抗病毒转录物的这种早期限制可能允许高病毒载量，以及随之而来的免疫失调，通常在SARS-CoV-2感染中可见。

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Ribosome-profiling reveals restricted post transcriptional ex-pression of antiviral cytokines and transcription factors during SARS-CoV-2 infection

The global COVID-19 pandemic caused by SARS-CoV-2 has resulted in over 2.2 million deaths. Disease outcomes range from asymptomatic to severe with, so far, minimal genotypic change to the virus so understanding the host response is paramount. Transcriptomics has become incredibly important in understanding host-pathogen interactions; however, post-transcriptional regulation plays an important role in infection and immunity through translation and mRNA stability, al-lowing tight control over potent host responses by both the host and the invading virus. Here we apply ribosome profiling to assess post-transcriptional regulation of host genes during SARS-CoV-2 infection of a human lung epithelial cell line (Calu-3). We have identified numerous transcription factors (JUN, ZBTB20, ATF3, HIVEP2 and EGR1) as well as select antiviral cytokine genes, namely IFNB1, IFNL1,2 and 3, IL-6 and CCL5, that are restricted at the post-transcriptional level by SARS-CoV-2 infection and discuss the impact this would have on the host response to infection. This early phase restriction of antiviral transcripts in the lungs may allow high viral load and consequent immune dysregulation typically seen in SARS-CoV-2 infection.

更新日期：2021-03-05

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