tetano
Editor, Senior Moderator
Emerg Microbes Infect
. 2024 Oct 22:2417868.
doi: 10.1080/22221751.2024.2417868. Online ahead of print. SARS-CoV-2 hijacks host CD55, CD59 and Factor H to impair antibody-dependent complement-mediated lysis
Laura Gebetsberger[SUP] 1 [/SUP], Zahra Malekshahi[SUP] 2 [/SUP], Aron Teutsch[SUP] 2 [/SUP], Gabor Tajti[SUP] 1 [/SUP], Frédéric Fontaine[SUP] 3 [/SUP], Nara Marella[SUP] 3 [/SUP], André Mueller[SUP] 3 [/SUP], Lena Prantl[SUP] 2 [/SUP], Hannes Stockinger[SUP] 1 [/SUP], Heribert Stoiber[SUP] 2 [/SUP], Anna Ohradanova-Repic[SUP] 1 [/SUP]
Affiliations
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 immunised 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).
Keywords: SARS-CoV-2; antiviral immunity; complement; immune evasion; regulators of complement activation.
. 2024 Oct 22:2417868.
doi: 10.1080/22221751.2024.2417868. Online ahead of print. SARS-CoV-2 hijacks host CD55, CD59 and Factor H to impair antibody-dependent complement-mediated lysis
Laura Gebetsberger[SUP] 1 [/SUP], Zahra Malekshahi[SUP] 2 [/SUP], Aron Teutsch[SUP] 2 [/SUP], Gabor Tajti[SUP] 1 [/SUP], Frédéric Fontaine[SUP] 3 [/SUP], Nara Marella[SUP] 3 [/SUP], André Mueller[SUP] 3 [/SUP], Lena Prantl[SUP] 2 [/SUP], Hannes Stockinger[SUP] 1 [/SUP], Heribert Stoiber[SUP] 2 [/SUP], Anna Ohradanova-Repic[SUP] 1 [/SUP]
Affiliations
- PMID: 39435487
- DOI: 10.1080/22221751.2024.2417868
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 immunised 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).
Keywords: SARS-CoV-2; antiviral immunity; complement; immune evasion; regulators of complement activation.