Bresson Stefan, Sani Emanuela, Armatowska Alicja, Dixon Charles, Tollervey David
Discovery Research Platform for Hidden Cell Biology, University of Edinburgh, Edinburgh, Scotland, UK.
Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
PLoS Pathog. 2025 Jan 27;21(1):e1012831. doi: 10.1371/journal.ppat.1012831. eCollection 2025 Jan.
The coronavirus HCoV-OC43 circulates continuously in the human population and is a frequent cause of the common cold. Here, we generated a high-resolution atlas of the transcriptional and translational landscape of OC43 during a time course following infection of human lung fibroblasts. Using ribosome profiling, we quantified the relative expression of the canonical open reading frames (ORFs) and identified previously unannotated ORFs. These included several potential short upstream ORFs and a putative ORF nested inside the M gene. In parallel, we analyzed the cellular response to infection. Endoplasmic reticulum (ER) stress response genes were transcriptionally and translationally induced beginning 12 and 18 hours post infection, respectively. By contrast, conventional antiviral genes mostly remained quiescent. At the same time points, we observed accumulation and increased translation of noncoding transcripts normally targeted by nonsense mediated decay (NMD), suggesting NMD is suppressed during the course of infection. This work provides resources for deeper understanding of OC43 gene expression and the cellular responses during infection.
冠状病毒HCoV-OC43在人群中持续传播，是引起普通感冒的常见原因。在此，我们绘制了人类肺成纤维细胞感染后随时间变化的OC43转录和翻译图谱的高分辨率图谱。利用核糖体谱分析，我们定量了经典开放阅读框（ORF）的相对表达，并鉴定了先前未注释的ORF。其中包括几个潜在的短上游ORF和一个嵌套在M基因内的假定ORF。同时，我们分析了细胞对感染的反应。内质网（ER）应激反应基因分别在感染后12小时和18小时开始在转录和翻译水平上被诱导。相比之下，传统的抗病毒基因大多保持静止。在相同的时间点，我们观察到通常被无义介导衰变（NMD）靶向的非编码转录本的积累和翻译增加，这表明在感染过程中NMD被抑制。这项工作为深入了解OC43基因表达和感染期间的细胞反应提供了资源。
