The Binding of the SARS-CoV-2 Spike Protein to Platelet Factor 4: A Proposed Mechanism for the Generation of Pathogenic Antibodies
Pathogenic platelet factor 4 (PF4) antibodies contributed to the abnormal coagulation profiles in COVID-19 and vaccinated patients. However, the mechanism of what triggers the body to produce these antibodies has not yet been clarified. Similar patterns and many comparable features between the COVID...
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| Format: | Article |
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MDPI AG
2024-02-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/14/3/245 |
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| author | Thi-Huong Nguyen Li-Yu Chen Nida Zaman Khan Annerose Lindenbauer Van-Chien Bui Peter F. Zipfel Doris Heinrich |
| author_facet | Thi-Huong Nguyen Li-Yu Chen Nida Zaman Khan Annerose Lindenbauer Van-Chien Bui Peter F. Zipfel Doris Heinrich |
| author_sort | Thi-Huong Nguyen |
| collection | DOAJ |
| description | Pathogenic platelet factor 4 (PF4) antibodies contributed to the abnormal coagulation profiles in COVID-19 and vaccinated patients. However, the mechanism of what triggers the body to produce these antibodies has not yet been clarified. Similar patterns and many comparable features between the COVID-19 virus and heparin-induced thrombocytopenia (HIT) have been reported. Previously, we identified a new mechanism of autoimmunity in HIT in which PF4-antibodies self-clustered PF4 and exposed binding epitopes for other pathogenic PF4/eparin antibodies. Here, we first proved that the SARS-CoV-2 spike protein (SP) also binds to PF4. The binding was evidenced by the increase in mass and optical intensity as observed through quartz crystal microbalance and immunosorbent assay, while the switching of the surface zeta potential caused by protein interactions and binding affinity of PF4-SP were evaluated by dynamic light scattering and isothermal spectral shift analysis. Based on our results, we proposed a mechanism for the generation of PF4 antibodies in COVID-19 patients. We further validated the changes in zeta potential and interaction affinity between PF4 and SP and found that their binding mechanism differs from ACE2–SP binding. Importantly, the PF4/SP complexes facilitate the binding of anti-PF4/Heparin antibodies. Our findings offer a fresh perspective on PF4 engagement with the SARS-CoV-2 SP, illuminating the role of PF4/SP complexes in severe thrombotic events. |
| first_indexed | 2024-04-24T18:30:13Z |
| format | Article |
| id | doaj.art-873f051a8c3447da842f270f84ddf12e |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-04-24T18:30:13Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-873f051a8c3447da842f270f84ddf12e2024-03-27T13:27:46ZengMDPI AGBiomolecules2218-273X2024-02-0114324510.3390/biom14030245The Binding of the SARS-CoV-2 Spike Protein to Platelet Factor 4: A Proposed Mechanism for the Generation of Pathogenic AntibodiesThi-Huong Nguyen0Li-Yu Chen1Nida Zaman Khan2Annerose Lindenbauer3Van-Chien Bui4Peter F. Zipfel5Doris Heinrich6Institute for Bioprocessing and Analytical Measurement Techniques (iba), 37308 Heilbad Heiligenstadt, GermanyInstitute for Bioprocessing and Analytical Measurement Techniques (iba), 37308 Heilbad Heiligenstadt, GermanyInstitute for Bioprocessing and Analytical Measurement Techniques (iba), 37308 Heilbad Heiligenstadt, GermanyInstitute for Bioprocessing and Analytical Measurement Techniques (iba), 37308 Heilbad Heiligenstadt, GermanyDepartment of Water Supply and Wastewater Treatment, Eichsfeldwerke GmbH, 37308 Heilbad Heiligenstadt, GermanyInstitute of Miccrobiology, Friedrich-Schiller-University, 07745 Jena, GermanyInstitute for Bioprocessing and Analytical Measurement Techniques (iba), 37308 Heilbad Heiligenstadt, GermanyPathogenic platelet factor 4 (PF4) antibodies contributed to the abnormal coagulation profiles in COVID-19 and vaccinated patients. However, the mechanism of what triggers the body to produce these antibodies has not yet been clarified. Similar patterns and many comparable features between the COVID-19 virus and heparin-induced thrombocytopenia (HIT) have been reported. Previously, we identified a new mechanism of autoimmunity in HIT in which PF4-antibodies self-clustered PF4 and exposed binding epitopes for other pathogenic PF4/eparin antibodies. Here, we first proved that the SARS-CoV-2 spike protein (SP) also binds to PF4. The binding was evidenced by the increase in mass and optical intensity as observed through quartz crystal microbalance and immunosorbent assay, while the switching of the surface zeta potential caused by protein interactions and binding affinity of PF4-SP were evaluated by dynamic light scattering and isothermal spectral shift analysis. Based on our results, we proposed a mechanism for the generation of PF4 antibodies in COVID-19 patients. We further validated the changes in zeta potential and interaction affinity between PF4 and SP and found that their binding mechanism differs from ACE2–SP binding. Importantly, the PF4/SP complexes facilitate the binding of anti-PF4/Heparin antibodies. Our findings offer a fresh perspective on PF4 engagement with the SARS-CoV-2 SP, illuminating the role of PF4/SP complexes in severe thrombotic events.https://www.mdpi.com/2218-273X/14/3/245SARS-CoV-2 spike proteinPF4PF4/SP antibodiesgenerationmechanism |
| spellingShingle | Thi-Huong Nguyen Li-Yu Chen Nida Zaman Khan Annerose Lindenbauer Van-Chien Bui Peter F. Zipfel Doris Heinrich The Binding of the SARS-CoV-2 Spike Protein to Platelet Factor 4: A Proposed Mechanism for the Generation of Pathogenic Antibodies Biomolecules SARS-CoV-2 spike protein PF4 PF4/SP antibodies generation mechanism |
| title | The Binding of the SARS-CoV-2 Spike Protein to Platelet Factor 4: A Proposed Mechanism for the Generation of Pathogenic Antibodies |
| title_full | The Binding of the SARS-CoV-2 Spike Protein to Platelet Factor 4: A Proposed Mechanism for the Generation of Pathogenic Antibodies |
| title_fullStr | The Binding of the SARS-CoV-2 Spike Protein to Platelet Factor 4: A Proposed Mechanism for the Generation of Pathogenic Antibodies |
| title_full_unstemmed | The Binding of the SARS-CoV-2 Spike Protein to Platelet Factor 4: A Proposed Mechanism for the Generation of Pathogenic Antibodies |
| title_short | The Binding of the SARS-CoV-2 Spike Protein to Platelet Factor 4: A Proposed Mechanism for the Generation of Pathogenic Antibodies |
| title_sort | binding of the sars cov 2 spike protein to platelet factor 4 a proposed mechanism for the generation of pathogenic antibodies |
| topic | SARS-CoV-2 spike protein PF4 PF4/SP antibodies generation mechanism |
| url | https://www.mdpi.com/2218-273X/14/3/245 |
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