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Staufer, Oskar ; Gupta, Kapil ; Hernandez Bücher, Jochen Estebano ; Kohler, Fabian ; Sigl, Christian ; Singh, Gunjita ; Vasileiou, Kate ; Yagüe Relimpio, Ana ; Macher, Meline ; Fabritz, Sebastian ; Dietz, Hendrik ; Cavalcanti-Adam, Elisabetta Ada ; Schaffitzel, Christiane ; Ruggieri, Alessia ; Platzman, Ilia ; Berger, Imre ; Spatz, Joachim P.:
Synthetic virions reveal fatty acid-coupled adaptive immunogenicity of SARS-CoV-2 spike glycoprotein.
In: Nature Communications.
Bd. 13
(2022)
Heft 1
.
- 868.
ISSN 2041-1723
DOI: https://doi.org/10.1038/s41467-022-28446-x
Abstract
SARS-CoV-2 infection is a major global public health concern with incompletely understood pathogenesis. The SARS-CoV-2 spike (S) glycoprotein comprises a highly conserved free fatty acid binding pocket (FABP) with unknown function and evolutionary selection advantage1,2. Deciphering FABP impact on COVID-19 progression is challenged by the heterogenous nature and large molecular variability of live virus. Here we create synthetic minimal virions (MiniVs) of wild-type and mutant SARS-CoV-2 with precise molecular composition and programmable complexity by bottom-up assembly. MiniV-based systematic assessment of S free fatty acid (FFA) binding reveals that FABP functions as an allosteric regulatory site enabling adaptation of SARS-CoV-2 immunogenicity to inflammation states via binding of pro-inflammatory FFAs. This is achieved by regulation of the S open-to-close equilibrium and the exposure of both, the receptor binding domain (RBD) and the SARS-CoV-2 RGD motif that is responsible for integrin co-receptor engagement. We find that the FDA-approved drugs vitamin K and dexamethasone modulate S-based cell binding in an FABP-like manner. In inflammatory FFA environments, neutralizing immunoglobulins from human convalescent COVID-19 donors lose neutralization activity. Empowered by our MiniV technology, we suggest a conserved mechanism by which SARS-CoV-2 dynamically couples its immunogenicity to the host immune response.
Weitere Angaben
| Publikationsform: | Artikel in einer Zeitschrift |
|---|---|
| Begutachteter Beitrag: | Ja |
| Institutionen der Universität: | Fakultäten > Fakultät für Ingenieurwissenschaften > Lehrstuhl Zelluläre Biomechanik > Lehrstuhl Zelluläre Biomechanik - Univ.-Prof. Dr. Dr. Elisabetta Ada Cavalcanti-Adam Fakultäten Fakultäten > Fakultät für Ingenieurwissenschaften Fakultäten > Fakultät für Ingenieurwissenschaften > Lehrstuhl Zelluläre Biomechanik |
| Titel an der UBT entstanden: | Nein |
| Themengebiete aus DDC: | 600 Technik, Medizin, angewandte Wissenschaften > 620 Ingenieurwissenschaften |
| Eingestellt am: | 07 Jun 2023 06:27 |
| Letzte Änderung: | 07 Jun 2023 06:27 |
| URI: | https://eref.uni-bayreuth.de/id/eprint/81235 |