TY - JOUR
AU - Lee, Jeffrey Y.
AU - Wang, Peter A.C.
AU - Gala, Dalia S.
AU - Noerenberg, Marko
AU - Järvelin, Aino I.
AU - Titlow, Joshua
AU - Zhuang, Xiaodong
AU - Palmalux, Natasha
AU - Iselin, Louisa
AU - Thompson, Mary Kay
AU - Parton, Richard M.
AU - Prange-Barczynska, Maria
AU - Wainman, Alan
AU - Salguero, Francisco J.
AU - Bishop, Tammie
AU - Agranoff, Daniel
AU - James, William
AU - Castello, Alfredo
AU - McKeating, Jane A.
AU - Davis, Ilan
PY - 2022
DA - January
TI - Absolute quantitation of individual SARS-CoV-2 RNA molecules provides a new paradigm for infection dynamics and variant differences
JO - eLife
VL - 11
DO - http://dx.doi.org/10.7554/eLife.74153
AB - 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.
PB - eLife Sciences Publications
UR - http://eprints.gla.ac.uk/261282/
KW - Coronavirus (COVID-19)
ER