Your browser doesn't support javascript.
Absolute quantitation of individual SARS-CoV-2 RNA molecules provides a new paradigm for infection dynamics and variant differences.
Lee, Jeffrey Y; Wing, Peter A C; Gala, Dalia S; Noerenberg, Marko; Järvelin, Aino I; Titlow, Joshua; Zhuang, Xiaodong; Palmalux, Natasha; Iselin, Louisa; Thompson, Mary Kay; Parton, Richard M; Prange-Barczynska, Maria; Wainman, Alan; Salguero, Francisco J; Bishop, Tammie; Agranoff, Daniel; James, William; Castello, Alfredo; McKeating, Jane A; Davis, Ilan.
  • Lee JY; Department of Biochemistry, The University of Oxford, Oxford, United Kingdom.
  • Wing PAC; Nuffield Department of Medicine, The University of Oxford, Oxford, United Kingdom.
  • Gala DS; Chinese Academy of Medical Sciences (CAMS) Oxford Institute (COI), The University of Oxford, Oxford, United Kingdom.
  • Noerenberg M; Department of Biochemistry, The University of Oxford, Oxford, United Kingdom.
  • Järvelin AI; Department of Biochemistry, The University of Oxford, Oxford, United Kingdom.
  • Titlow J; MRC-University of Glasgow Centre for Virus Research, The University of Glasgow, Glasgow, United Kingdom.
  • Zhuang X; Department of Biochemistry, The University of Oxford, Oxford, United Kingdom.
  • Palmalux N; Department of Biochemistry, The University of Oxford, Oxford, United Kingdom.
  • Iselin L; Nuffield Department of Medicine, The University of Oxford, Oxford, United Kingdom.
  • Thompson MK; MRC-University of Glasgow Centre for Virus Research, The University of Glasgow, Glasgow, United Kingdom.
  • Parton RM; Department of Biochemistry, The University of Oxford, Oxford, United Kingdom.
  • Prange-Barczynska M; Department of Biochemistry, The University of Oxford, Oxford, United Kingdom.
  • Wainman A; Department of Biochemistry, The University of Oxford, Oxford, United Kingdom.
  • Salguero FJ; Nuffield Department of Medicine, The University of Oxford, Oxford, United Kingdom.
  • Bishop T; Ludwig Institute for Cancer Research, The University of Oxford, Oxford, United Kingdom.
  • Agranoff D; Sir William Dunn School of Pathology, The University of Oxford, Oxford, United Kingdom.
  • James W; UK Health Security Agency, UKHSA-Porton Down, Salisbury, United Kingdom.
  • Castello A; Nuffield Department of Medicine, The University of Oxford, Oxford, United Kingdom.
  • McKeating JA; Ludwig Institute for Cancer Research, The University of Oxford, Oxford, United Kingdom.
  • Davis I; Department of Infectious Diseases, University Hospitals Sussex NHS Foundation Trust, Brighton, United Kingdom.
Elife ; 112022 01 20.
Article in English | MEDLINE | ID: covidwho-1634530
ABSTRACT
Despite an unprecedented global research effort on SARS-CoV-2, early replication events remain poorly understood. Given the clinical importance of emergent viral variants with increased transmission, there is an urgent need to understand the early stages of viral replication and transcription. We used single-molecule fluorescence in situ hybridisation (smFISH) to quantify positive sense RNA genomes with 95% detection efficiency, while simultaneously visualising negative sense genomes, subgenomic RNAs, and viral proteins. Our absolute quantification of viral RNAs and replication factories revealed that SARS-CoV-2 genomic RNA is long-lived after entry, suggesting that it avoids degradation by cellular nucleases. Moreover, we observed that SARS-CoV-2 replication is highly variable between cells, with only a small cell population displaying high burden of viral RNA. Unexpectedly, the B.1.1.7 variant, first identified in the UK, exhibits significantly slower replication kinetics than the Victoria strain, suggesting a novel mechanism contributing to its higher transmissibility with important clinical implications.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: RNA, Viral / SARS-CoV-2 / COVID-19 Type of study: Prognostic study Topics: Variants Limits: Animals Language: English Year: 2022 Document Type: Article Affiliation country: ELife.74153

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: RNA, Viral / SARS-CoV-2 / COVID-19 Type of study: Prognostic study Topics: Variants Limits: Animals Language: English Year: 2022 Document Type: Article Affiliation country: ELife.74153