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http://conacyt.repositorioinstitucional.mx/jspui/handle/1000/8465| Temperature impacts SARS-CoV-2 spike fusogenicity and evolution | |
| Jérémy Dufloo Rafael Sanjuan | |
| Acceso Abierto | |
| Atribución-NoComercial-SinDerivadas | |
| https://doi.org/10.1101/2023.12.20.572501 | |
| https://www.biorxiv.org/content/10.1101/2023.12.20.572501v1 | |
| SARS-CoV-2 infects both the upper and lower respiratory tracts, which are characterized by different temperatures (33°C and 37°C, respectively). In addition, fever is a common COVID-19 symptom. SARS-CoV-2 has been shown to replicate more efficiently at low temperatures but the effect of temperature on different viral proteins remains poorly understood. Here, we investigate how temperature affects the SARS-CoV-2 spike function and evolution. We first observed that rising temperature from 33°C to 37°C or 39°C increased spike-mediated cell-cell fusion. We then experimentally evolved a recombinant vesicular stomatitis virus expressing the SARS-CoV-2 spike at these different temperatures. We found that spike-mediated cell-cell fusion was maintained during evolution at 39°C, but was lost in a high proportion of viruses evolved at 33°C or 37°C. Consistently, sequencing of the spikes evolved at 33°C or 37°C revealed the accumulation of mutations around the furin cleavage site, a region that determines cell-cell fusion, whereas this did not occur in spikes evolved at 39°C. Finally, using site-directed mutagenesis, we found that disruption of the furin cleavage site had a temperature-dependent effect on spike-induced cell-cell fusion and viral fitness. Our results suggest that variations in body temperature may affect the activity and diversification of the SARS-CoV-2 spike. Importance When it infects humans, SARS-CoV-2 is exposed to different temperaures (e.g. replication site, fever…). Temperature has been shown to strongly impact SARS-CoV-2 replication but how it affects the activity and evolution of the spike protein remains poorly understood. Here, we first show that high temperatures increase the SARS-CoV-2 spike fusogenicity. Then, we demonstrate that the evolution of the spike activity and variants depends on temperature. Finally, we show that the functional effect of specific spike mutations is temperature-dependent. Overall, our results suggest that temperature may be a factor influencing the activity and adapatation of the SARS-CoV-2 spike in vivo, which will help understanding viral tropism, pathogenesis, and evolution. | |
| bioRxiv | |
| 20-12-2023 | |
| Preimpreso | |
| Inglés | |
| Público en general | |
| VIRUS RESPIRATORIOS | |
| Aparece en las colecciones: | Materiales de Consulta y Comunicados Técnicos |
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| Temperature impacts SARS-CoV-2 spike fusogenicity and evolution.pdf | 1.49 MB | Adobe PDF | Visualizar/Abrir |