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



Dong, Xiaofeng, Penrice-Randal, Rebekah ORCID: 0000-0002-0653-2097, Goldswain, Hannah, Prince, Tessa, Randle, Nadine, Salguero, Javier, Tree, Julia, Vamos, Ecaterina, Nelson, Charlotte, Stewart, James ORCID: 0000-0002-8928-2037
et al (show 10 more authors) (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-.

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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 and Life Sciences
Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User: Symplectic Admin
Date Deposited: 09 Apr 2021 08:17
Last Modified: 14 Mar 2024 18:09
DOI: 10.1101/2021.03.03.433753
Open Access URL: http://doi.org/10.1101/2021.03.03.433753
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3118757