Transcriptional Difference between SARS-COV-2 and other Human Coronaviruses Revealed by Sub-genomic RNA Profiling

Lv, Lin; Xie, Xiaoqing; Gong, Qiyu; Feng, Ru; Guo, Xiaokui; Su, Bing; Chen, Lei

SARS-COV-2 and all other coronaviruses express its 3 prime genes by forming sub-genomic RNA. As the genome of these virus exist in RNA form, only by profiling the relative abundance of these sgRNAs, can the viral transcriptome be revealed. Utilizing publically available meta-transcriptomic data generated from patient samples, we were able to infer the viral transcriptome in vivo, which is distinct from the in vitro one derived from cell culture. Inter-sample diversity was also observed and a sample specific transcript was identified. By doing the same analysis to MERS and SARS data, we were able to compare the three in terms of transcription. Among the differences, SARS-COV-2 has significantly elevated expression of the Spike gene, which may contribute to its high transmissibility. Highlights The in vivo transcriptome of SARS-CoV-2 revealed by sgRNA profiling, for 25 patient samples around the globe. The Spike protein expression is an order of magnitude higher in SARS-CoV-2 than MERS-CoV or SARS-CoV, possibly contributing to the virus’ elevated transmissibility. The in vivo SARS-CoV-2 transcriptomes, as inferred from human patient data was distinct from the in vitro one derived from cell line culture, all the accessory genes were up-regulated in vivo, suggesting intricate expression regulation mechanism for the small viral genome.