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

Autor: Javier Salguero, Charlotte Nelson, Peter J. M. Openshaw, Isaric C Investigators, David A. Matthews, Miles W. Carroll, Hannah Goldswain, Tessa Prince, Rebekah Penrice-Randal, Malcolm G Semple, Alistair C. Darby, Xiaofeng Dong, James P. Stewart, Julian A. Hiscox, Julia A. Tree, Ecaterina Vamos, Lance Turtle, Kenneth Baillie, Nadine Randle
Rok vydání: 2021
Předmět:
DOI: 10.1101/2021.03.03.433753
Popis: 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.
Databáze: OpenAIRE