Researchers have unveiled that SARS-CoV-2 takes control of three key host proteins, which hinder the function of the complement system—an essential part of the body’s initial antiviral defense. This interference greatly reduces the virus’s elimination, potentially influencing both immediate COVID-19 cases and ongoing symptoms that arise after the infection.
A team from the Medical University of Vienna and the Medical University of Innsbruck has found that SARS-CoV-2 commandeers three crucial host proteins that inhibit the complement system, a vital aspect of early antiviral defense. This action significantly hampers the virus’s clearance and may impact the progression of both acute COVID-19 cases and post-COVID-19 complications. Their findings were recently published in the journal Emerging Microbes & Infections.
An effective and prompt immune response is vital for overcoming viral infections and avoiding complications that follow. The complement system, a crucial part of antiviral immunity, consists of a series of proteins present in blood and at mucosal surfaces like the respiratory tract. It is activated through three distinct pathways, enabling the clearance of virus particles by directly destroying them (lysis). To prevent unintentional harm to host cells, complement activity is quickly inhibited by host molecules known as complement regulatory proteins. The recent study, led by Anna Ohradanova-Repic and her team from the Center for Pathophysiology, Infectiology and Immunology at the Medical University of Vienna, in collaboration with Heribert Stoiber’s team from the Institute of Virology at the Medical University of Innsbruck, reveals that SARS-CoV-2 appropriates three of these regulatory proteins: CD55, CD59, and Factor H, effectively protecting itself from destruction by the complement system.
Utilizing host proteins for enhanced resistance to complement
By cultivating SARS-CoV-2 in human cells, the researchers found that the virus particles absorb the host proteins CD55 and CD59. Further investigations indicated that SARS-CoV-2 also interacts with Factor H, another regulatory protein primarily located in the blood. When the virus particles were exposed to active complement, it was observed that they were somewhat resistant to complement-triggered lysis. By eliminating CD55, CD59, and Factor H from the virus’s surface or blocking their functions, the researchers managed to reinstate the ability of the complement system to clear SARS-CoV-2 effectively.
“By seizing these three proteins, SARS-CoV-2 evades the three complement pathways, leading to a reduction or delay in the host’s ability to clear the virus,” explains Anna Ohradanova-Repic, the study’s lead author. Since the complement system is closely tied to other aspects of the immune response, this not only hinders the elimination of the virus but can also provoke significant inflammation, a major characteristic of both severe COVID-19 and Long COVID.
“Revealing these immune evasion strategies that allow the virus to persist longer in the host enhances our knowledge of both the immediate and lasting effects of SARS-CoV-2 infection,” says Laura Gebetsberger, the first author of the study.
