Temperature impacts SARS-CoV-2 spike fusogenicity and evolution
ABSTRACTSARS-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 tem...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2024-04-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mbio.03360-23 |
| _version_ | 1797215311655600128 |
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| author | Jérémy Dufloo Rafael Sanjuán |
| author_facet | Jérémy Dufloo Rafael Sanjuán |
| author_sort | Jérémy Dufloo |
| collection | DOAJ |
| description | ABSTRACTSARS-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 increasing 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 that 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.IMPORTANCEWhen it infects humans, SARS-CoV-2 is exposed to different temperatures (e.g., replication site and 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 adaptation of the SARS-CoV-2 spike in vivo, which will help understanding viral tropism, pathogenesis, and evolution. |
| first_indexed | 2024-04-24T11:28:03Z |
| format | Article |
| id | doaj.art-b8d1379682d1474ba2130cacecb1714f |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-04-24T11:28:03Z |
| publishDate | 2024-04-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-b8d1379682d1474ba2130cacecb1714f2024-04-10T13:01:15ZengAmerican Society for MicrobiologymBio2150-75112024-04-0115410.1128/mbio.03360-23Temperature impacts SARS-CoV-2 spike fusogenicity and evolutionJérémy Dufloo0Rafael Sanjuán1Institute for Integrative Systems Biology, Consejo Superior de Investigaciones Científicas-Universitat de València, Paterna, València, SpainInstitute for Integrative Systems Biology, Consejo Superior de Investigaciones Científicas-Universitat de València, Paterna, València, SpainABSTRACTSARS-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 increasing 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 that 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.IMPORTANCEWhen it infects humans, SARS-CoV-2 is exposed to different temperatures (e.g., replication site and 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 adaptation of the SARS-CoV-2 spike in vivo, which will help understanding viral tropism, pathogenesis, and evolution.https://journals.asm.org/doi/10.1128/mbio.03360-23SARS-CoV-2 spiketemperatureexperimental evolutioncell-to-cell fusionSARS-CoV-2 variants |
| spellingShingle | Jérémy Dufloo Rafael Sanjuán Temperature impacts SARS-CoV-2 spike fusogenicity and evolution mBio SARS-CoV-2 spike temperature experimental evolution cell-to-cell fusion SARS-CoV-2 variants |
| title | Temperature impacts SARS-CoV-2 spike fusogenicity and evolution |
| title_full | Temperature impacts SARS-CoV-2 spike fusogenicity and evolution |
| title_fullStr | Temperature impacts SARS-CoV-2 spike fusogenicity and evolution |
| title_full_unstemmed | Temperature impacts SARS-CoV-2 spike fusogenicity and evolution |
| title_short | Temperature impacts SARS-CoV-2 spike fusogenicity and evolution |
| title_sort | temperature impacts sars cov 2 spike fusogenicity and evolution |
| topic | SARS-CoV-2 spike temperature experimental evolution cell-to-cell fusion SARS-CoV-2 variants |
| url | https://journals.asm.org/doi/10.1128/mbio.03360-23 |
| work_keys_str_mv | AT jeremydufloo temperatureimpactssarscov2spikefusogenicityandevolution AT rafaelsanjuan temperatureimpactssarscov2spikefusogenicityandevolution |