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 dysregulation at later time points that can also be identified in humans

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Dong, Xiaofeng, Penrice-Randal, Rebekah ORCID: 0000-0002-0653-2097, Goldswain, Hannah ORCID: 0000-0003-4194-8714, Prince, Tessa ORCID: 0000-0002-8796-2629, Randle, Nadine ORCID: 0000-0002-3775-9585, Salguero, Javier, Tree, Julia ORCID: 0000-0002-1720-6764, Vamos, Ecaterina, Nelson, Charlotte, Stewart, James ORCID: 0000-0002-8928-2037 et al (show 10 more authors) , ISARIC4C Investigators ORCID: 0000-0001-9700-0418, COVID-19 Genomics UK (COG-UK) Consortium, Semple, Malcolm ORCID: 0000-0001-9700-0418, Baillie, Kenneth ORCID: 0000-0001-5258-793X, Openshaw, Peter, Turtle, Lance ORCID: 0000-0002-0778-1693, Matthews, David, Carroll, Miles, Darby, Alistair ORCID: 0000-0002-3786-6209 and Hiscox, Julian ORCID: 0000-0002-6582-0275 (2021) 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 dysregulation at later time points that can also be identified in humans bioRxiv. 2021.03.03.433753-. ISSN 2692-8205

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Abstract

<h4>Introduction</h4> 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. <h4>Results</h4> 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. <h4>Discussion</h4> 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.

Item Type:	Article
Uncontrolled Keywords:	ISARIC4C Investigators, COVID-19 Genomics UK (COG-UK) Consortium
Divisions:	Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Infection, Vet & Ecological Sciences
Depositing User:	Symplectic Admin
Date Deposited:	09 Apr 2021 08:17
Last Modified:	29 May 2026 06:51
DOI:	10.1101/2021.03.03.433753
Open Access URL:	http://doi.org/10.1101/2021.03.03.433753
Related Websites:	Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3118757
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