Identification and quantification of SARS-CoV-2 leader subgenomic mRNA gene junctions in nasopharyngeal samples shows phasic transcription in animal models of COVID-19 and aberrant pattens in humans

Penrice-Randal, R.; Goldswain, H.; Prince, T.; Randle, N.; Salguero, J.; Tree, J.; Vamos, E.; Nelson, C.; ISARIC-4C Investigators,; COG-UK Consortium,; Stewart, J. P.; Matthews, D. A.; Carroll, M.; Darby, A.; Hiscox, J. A.

doi:10.1101/2021.03.03.433753

bioRxiv · 10.1101/2021.03.03.433753

Identification and quantification of SARS-CoV-2 leader subgenomic mRNA gene junctions in nasopharyngeal samples shows phasic transcription in animal models of COVID-19 and aberrant pattens in humans

Penrice-Randal, R.·Goldswain, H.·Prince, T.·Randle, N.·Salguero, J.·Tree, J.·Vamos, E.·Nelson, C.·ISARIC-4C Investigators,·COG-UK Consortium,·Stewart, J. P.·Matthews, D. A.·Carroll, M.·Darby, A.·Hiscox, J. A.

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Abstract

IntroductionSARS-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. ResultsHigh 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. DiscussionLeTRS 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.

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Penrice-Randal, R., Goldswain, H., Prince, T., Randle, N., Salguero, J., Tree, J., Vamos, E., Nelson, C., ISARIC-4C Investigators,, COG-UK Consortium,, Stewart, J. P., Matthews, D. A., Carroll, M., Darby, A., Hiscox, J. A.. 2021-03-03. Identification and quantification of SARS-CoV-2 leader subgenomic mRNA gene junctions in nasopharyngeal samples shows phasic transcription in animal models of COVID-19 and aberrant pattens in humans. https://doi.org/10.1101/2021.03.03.433753

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