SARS-CoV-2 hijacks host CD55, CD59 and factor H to impair antibody-dependent complement-mediated lysis
The complement system is a vital anti-microbial defence mechanism against circulating pathogens. Excessive complement activation can have deleterious outcomes for the host and is consequently tightly modulated by a set of membrane-associated and fluid-phase regulators of complement activation (RCAs)...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Emerging Microbes and Infections |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2024.2417868 |
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| author | Laura Gebetsberger Zahra Malekshahi Aron Teutsch Gabor Tajti Frédéric Fontaine Nara Marella André Mueller Lena Prantl Hannes Stockinger Heribert Stoiber Anna Ohradanova-Repic |
| author_facet | Laura Gebetsberger Zahra Malekshahi Aron Teutsch Gabor Tajti Frédéric Fontaine Nara Marella André Mueller Lena Prantl Hannes Stockinger Heribert Stoiber Anna Ohradanova-Repic |
| author_sort | Laura Gebetsberger |
| collection | DOAJ |
| description | The complement system is a vital anti-microbial defence mechanism against circulating pathogens. Excessive complement activation can have deleterious outcomes for the host and is consequently tightly modulated by a set of membrane-associated and fluid-phase regulators of complement activation (RCAs). Here, we demonstrate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijacks host cellular RCA members CD55 and CD59 and serum-derived Factor H (FH) to resist antibody-dependent complement-mediated lysis triggered by immunized human sera. Blockage of the biological functions of virion-associated CD55 and CD59 and competition of FH recruitment with functionally inactive recombinant FH-derived short consensus repeats SCR18-20 restore SARS-CoV-2 complement sensitivity in a synergistic manner. Moreover, complement-mediated virolysis is dependent on classical pathway activation and does not occur in the absence of virus-specific antibodies. Altogether, our findings present an intriguing immune escape mechanism that provides novel insights into the immunopathology observed in severe coronavirus disease 2019 (COVID-19). |
| format | Article |
| id | doaj-art-813767f8302d4d5094f5288e0c63c8f2 |
| institution | OA Journals |
| issn | 2222-1751 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj-art-813767f8302d4d5094f5288e0c63c8f22025-08-20T02:20:37ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512024-12-0113110.1080/22221751.2024.2417868SARS-CoV-2 hijacks host CD55, CD59 and factor H to impair antibody-dependent complement-mediated lysisLaura Gebetsberger0Zahra Malekshahi1Aron Teutsch2Gabor Tajti3Frédéric Fontaine4Nara Marella5André Mueller6Lena Prantl7Hannes Stockinger8Heribert Stoiber9Anna Ohradanova-Repic10Medical University of Vienna, Center for Pathophysiology, Infectiology and Immunology, Institute for Hygiene and Applied Immunology, Vienna, AustriaMedical University of Innsbruck, Institute of Virology, Innsbruck, AustriaMedical University of Innsbruck, Institute of Virology, Innsbruck, AustriaMedical University of Vienna, Center for Pathophysiology, Infectiology and Immunology, Institute for Hygiene and Applied Immunology, Vienna, AustriaCeMM – Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, AustriaCeMM – Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, AustriaCeMM – Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, AustriaMedical University of Innsbruck, Institute of Virology, Innsbruck, AustriaMedical University of Vienna, Center for Pathophysiology, Infectiology and Immunology, Institute for Hygiene and Applied Immunology, Vienna, AustriaMedical University of Innsbruck, Institute of Virology, Innsbruck, AustriaMedical University of Vienna, Center for Pathophysiology, Infectiology and Immunology, Institute for Hygiene and Applied Immunology, Vienna, AustriaThe complement system is a vital anti-microbial defence mechanism against circulating pathogens. Excessive complement activation can have deleterious outcomes for the host and is consequently tightly modulated by a set of membrane-associated and fluid-phase regulators of complement activation (RCAs). Here, we demonstrate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijacks host cellular RCA members CD55 and CD59 and serum-derived Factor H (FH) to resist antibody-dependent complement-mediated lysis triggered by immunized human sera. Blockage of the biological functions of virion-associated CD55 and CD59 and competition of FH recruitment with functionally inactive recombinant FH-derived short consensus repeats SCR18-20 restore SARS-CoV-2 complement sensitivity in a synergistic manner. Moreover, complement-mediated virolysis is dependent on classical pathway activation and does not occur in the absence of virus-specific antibodies. Altogether, our findings present an intriguing immune escape mechanism that provides novel insights into the immunopathology observed in severe coronavirus disease 2019 (COVID-19).https://www.tandfonline.com/doi/10.1080/22221751.2024.2417868SARS-CoV-2complementregulators of complement activationimmune evasionantiviral immunity |
| spellingShingle | Laura Gebetsberger Zahra Malekshahi Aron Teutsch Gabor Tajti Frédéric Fontaine Nara Marella André Mueller Lena Prantl Hannes Stockinger Heribert Stoiber Anna Ohradanova-Repic SARS-CoV-2 hijacks host CD55, CD59 and factor H to impair antibody-dependent complement-mediated lysis Emerging Microbes and Infections SARS-CoV-2 complement regulators of complement activation immune evasion antiviral immunity |
| title | SARS-CoV-2 hijacks host CD55, CD59 and factor H to impair antibody-dependent complement-mediated lysis |
| title_full | SARS-CoV-2 hijacks host CD55, CD59 and factor H to impair antibody-dependent complement-mediated lysis |
| title_fullStr | SARS-CoV-2 hijacks host CD55, CD59 and factor H to impair antibody-dependent complement-mediated lysis |
| title_full_unstemmed | SARS-CoV-2 hijacks host CD55, CD59 and factor H to impair antibody-dependent complement-mediated lysis |
| title_short | SARS-CoV-2 hijacks host CD55, CD59 and factor H to impair antibody-dependent complement-mediated lysis |
| title_sort | sars cov 2 hijacks host cd55 cd59 and factor h to impair antibody dependent complement mediated lysis |
| topic | SARS-CoV-2 complement regulators of complement activation immune evasion antiviral immunity |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2024.2417868 |
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