Abstract
Introduction SARS-CoV-2 has a complex strategy for the transcription of viral subgenomic mRNAs (sgmRNAs), which are targets for nucleic acid diagnostics. Each of these sgRNAs has a unique 5’ sequence, the leader-transcriptional regulatory sequence gene junction (leader-TRS-junction), that can be identified using sequencing.
Results High resolution sequencing has been used to investigate the biology of SARS-CoV-2 and the host response in cell culture models and from clinical samples. LeTRS, a bioinformatics tool, was developed to identify leader-TRS-junctions and be used as a proxy to quantify sgmRNAs for understanding virus biology. This was tested on published datasets and clinical samples from patients and longitudinal samples from animal models with COVID-19.
Discussion LeTRS identified known leader-TRS-junctions and identified novel species that were common across different species. The data indicated multi-phasic abundance of sgmRNAs in two different animal models, with spikes in sgmRNA abundance reflected in human samples, and therefore has implications for transmission models and nucleic acid-based diagnostics.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
1. Inclusion of COG-UK and ISARIC4C consortium authors. 2. More clarity in the Methods section. 3. Clarity of discussion and concluding statements. 4. Change of title to more accurately reflect the work and spelling mistake in the original title. 5. Inclusion of funders supporting the gathering of ISARIC4C samples. Updated FDA funding statement.