The transcriptional and translational landscape of HCoV-OC43 infection
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 at various timepoints following infection of human lung fibroblasts. Using ribosome profiling, we quantified the relative expression of the canonical open reading frames (ORFs) and identified several unannotated ORFs, including 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 are transcriptionally and translationally induced, but conventional antiviral genes remain mostly suppressed. At the same time, we observed widespread aberrant translation across cellular transcripts, including over 3'UTRs and of noncoding transcripts normally targeted by the nonsense mediated decay pathway. Taken together, our work provides a genomic resource for further study of OC43 and the cellular response to infection. Overall design: Human lung fibroblast (MRC5) cells were infected with the coronavirus OC43, and samples were collected for transcriptomic (RNAseq) and translatomic (Riboseq) analysis at various timepoints following infection.