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Temperature impacts SARS-CoV-2 spike fusogenicity and evolution.
Jérémy Dufloo1, Rafael Sanjuán1
1Institute for Integrative Systems Biology, Consejo Superior de Investigaciones Científicas-Universitat de València, Paterna, València, Spain.
Mbio
|February 27, 2024
Summary
Body temperature influences SARS-CoV-2 spike protein function and evolution. Higher temperatures enhance spike fusogenicity and maintain its activity during viral evolution, suggesting temperature impacts viral adaptation.
Area of Science:
- Virology
- Molecular Biology
- Infectious Diseases
Background:
- SARS-CoV-2 infects respiratory tracts at varying temperatures (33°C-37°C).
- COVID-19 symptoms include fever, indicating temperature fluctuations.
- Viral replication efficiency is temperature-dependent, but spike protein's response is unclear.
Purpose of the Study:
- Investigate temperature's effect on SARS-CoV-2 spike protein function and evolution.
- Determine if spike mutations' effects are temperature-dependent.
- Understand temperature's role in viral tropism, pathogenesis, and adaptation.
Main Methods:
- Measured spike-mediated cell-cell fusion at different temperatures (33°C, 37°C, 39°C).
- Experimentally evolved a recombinant virus expressing SARS-CoV-2 spike at varying temperatures.
- Sequenced spike proteins and used site-directed mutagenesis to analyze mutations.
Main Results:
- Increased temperature enhanced spike-mediated cell-cell fusion.
- Spike fusogenicity was maintained at 39°C during viral evolution, but lost at 33°C/37°C.
- Mutations accumulated near the furin cleavage site at lower temperatures, affecting fusion and fitness.
Conclusions:
- Temperature significantly influences SARS-CoV-2 spike protein activity and evolution.
- Higher temperatures promote spike fusogenicity and evolutionary stability.
- Temperature-dependent effects of spike mutations impact viral adaptation in vivo.
