Novel RT-ddPCR assays for measuring the levels of subgenomic and genomic SARS-CoV-2 transcripts

Methods. 2022 May:201:15-25. doi: 10.1016/j.ymeth.2021.04.011. Epub 2021 Apr 18.

Abstract

The replication of SARS-CoV-2 and other coronaviruses depends on transcription of negative-sense RNA intermediates that serve as the templates for the synthesis of positive-sense genomic RNA (gRNA) and multiple different subgenomic mRNAs (sgRNAs) encompassing fragments arising from discontinuous transcription. Recent studies have aimed to characterize the expression of subgenomic SARS-CoV-2 transcripts in order to investigate their clinical significance. Here, we describe a novel panel of reverse transcription droplet digital PCR (RT-ddPCR) assays designed to specifically quantify multiple different subgenomic SARS-CoV-2 transcripts and distinguish them from transcripts that do not arise from discontinuous transcription at each locus. These assays can be applied to samples from SARS-CoV-2 infected patients to better understand the regulation of SARS-CoV-2 transcription and how different sgRNAs may contribute to viral pathogenesis and clinical disease severity.

Keywords: COVID-19; Coronavirus; Digital PCR; Droplet digital PCR; Quantitative assays; SARS-CoV-2; Subgenomic RNA; Viral transcription/replication.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • COVID-19* / genetics
  • Humans
  • Polymerase Chain Reaction
  • RNA, Messenger / genetics
  • RNA, Viral / analysis
  • RNA, Viral / genetics
  • Reverse Transcription
  • SARS-CoV-2* / genetics

Substances

  • RNA, Messenger
  • RNA, Viral