Lee, J. Y. et al. (2022) Absolute quantitation of individual SARS-CoV-2 RNA molecules provides a new paradigm for infection dynamics and variant differences. eLife, 11, e74153. (doi: 10.7554/eLife.74153) (PMID:35049501) (PMCID:PMC8776252)
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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.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Palmalux, Natasha and Castello, Professor Alfredo and Iselin, Louisa and Noerenberg, Dr Marko |
| Creator Roles: | Noerenberg, M.Conceptualization, Formal analysis, Methodology, Resources Palmalux, N.Investigation, Methodology Iselin, L.Investigation, Methodology Castello, A.Conceptualization, Funding acquisition, Investigation, Methodology, Project administration, Supervision, Writing – original draft, Writing – review and editing |
| Authors: | Lee, J. Y., Wang, P. A.C., Gala, D. S., Noerenberg, M., Järvelin, A. I., Titlow, J., Zhuang, X., Palmalux, N., Iselin, L., Thompson, M. K., Parton, R. M., Prange-Barczynska, M., Wainman, A., Salguero, F. J., Bishop, T., Agranoff, D., James, W., Castello, A., McKeating, J. A., and Davis, I. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research |
| Journal Name: | eLife |
| Publisher: | eLife Sciences Publications |
| ISSN: | 2050-084X |
| ISSN (Online): | 2050-084X |
| Copyright Holders: | Copyright © 2022 Lee et al. |
| First Published: | First published in eLife 11: e74153 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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