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SARS-CoV-2 'steals' our proteins to protect itself from the immune system

Virus hijacks three important host proteins that dampen the activity of the complement system

Date:
November 8, 2024
Source:
Medical University of Vienna
Summary:
Researchers have discovered that SARS-CoV-2 hijacks three important host proteins that dampen the activity of the complement system, a key component of early antiviral immunity. This significantly impairs viral clearance which may affect the course of both acute COVID-19 infections and post-COVID-19 sequelae.
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Researchers at the Medical University of Vienna and the Medical University of Innsbruck discovered that SARS-CoV-2 hijacks three important host proteins that dampen the activity of the complement system, a key component of early antiviral immunity. This significantly impairs viral clearance which may affect the course of both acute COVID-19 infections and post-COVID-19 sequelae. The study was recently published in the journal Emerging Microbes & Infections.

An early and effective immune response is crucial for resolving viral infections and preventing post-infectious complications. The complement system, a pivotal element of antiviral immunity, is a cascade of proteins found in the bloodstream and at mucosal sites, such as the respiratory tract. Activated through three different pathways, complement facilitates the clearance of virus particles by directly inducing their destruction (lysis). To prevent bystander damage to host cells, complement is rapidly inactivated by a set of host molecules referred to as complement regulatory proteins. The new study led by Anna Ohradanova-Repic and colleagues from the Center for Pathophysiology, Infectiology and Immunology at the Medical University of Vienna in collaboration with the team of Heribert Stoiber from the Institute of Virology at the Medical University of Innsbruck shows that SARS-CoV-2 hijacks three of these regulatory proteins, CD55, CD59 and Factor H, and thereby successfully shields itself from complement-mediated lysis.

Hijacking host proteins for effective complement resistance

By propagating SARS-CoV-2 in human cells the researchers discovered that the virus particles acquire the cellular proteins CD55 and CD59. Further experiments showed that SARS-CoV-2 also binds to Factor H, another complement regulatory protein that is primarily found in the bloodstream. Confronting the virus particles with active complement revealed that they are partially resistant to complement-mediated lysis. By removing CD55, CD59 and Factor H from the virus surface or inhibiting their biological functions, the researchers could successfully restore complement-mediated clearance of SARS-CoV-2.

"Through hijacking these three proteins, SARS-CoV-2 can evade all three complement pathways, resulting in reduced or delayed viral clearance by the infected host," Anna Ohradanova-Repic, the leader of the study explains. Because complement is intricately linked with other components of the immune system, this not only affects virus elimination but can also cause significant inflammation, a core feature of both severe COVID-19 and Long COVID.

"Uncovering immune evasion mechanisms that allow the virus to linger within the host for longer, deepen our understanding of the acute and long-term impacts of SARS-CoV-2 infection," says first author Laura Gebetsberger.


Story Source:

Materials provided by Medical University of Vienna. Note: Content may be edited for style and length.


Journal Reference:

  1. 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 & Infections, 2024; 13 (1) DOI: 10.1080/22221751.2024.2417868

Cite This Page:

Medical University of Vienna. "SARS-CoV-2 'steals' our proteins to protect itself from the immune system." ScienceDaily. ScienceDaily, 8 November 2024. <www.sciencedaily.com/releases/2024/11/241108113712.htm>.
Medical University of Vienna. (2024, November 8). SARS-CoV-2 'steals' our proteins to protect itself from the immune system. ScienceDaily. Retrieved December 20, 2024 from www.sciencedaily.com/releases/2024/11/241108113712.htm
Medical University of Vienna. "SARS-CoV-2 'steals' our proteins to protect itself from the immune system." ScienceDaily. www.sciencedaily.com/releases/2024/11/241108113712.htm (accessed December 20, 2024).

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