The researchers at the Medical University of Vienna and the Medical University of Innsbruck have found that SARS-CoV-2, the virus that causes COVID-19, hijacks three important host proteins that dampen the activity of the complement system, a crucial part of the early antiviral immune response. This allows the virus to shield itself from complement-mediated lysis, impairing viral clearance and potentially affecting the course of both acute COVID-19 infections and post-COVID-19 sequelae. The study, published in Emerging Microbes & Infections, sheds light on the mechanisms the virus uses to evade the immune system and persist within the host.
The complement system is a cascade of proteins that plays a vital role in antiviral immunity by facilitating the clearance of virus particles through direct destruction. However, to prevent damage to host cells, the complement system is rapidly inactivated by host molecules known as complement regulatory proteins. The researchers found that SARS-CoV-2 hijacks three of these regulatory proteins – CD55, CD59, and Factor H – to shield itself from complement-mediated lysis. This evasion mechanism allows the virus to evade all three complement pathways, leading to reduced or delayed viral clearance by the infected host.
Through experiments propagating SARS-CoV-2 in human cells, the researchers observed that the virus particles acquire the cellular proteins CD55 and CD59, as well as bind to Factor H, a complement regulatory protein found in the bloodstream. When the virus particles were confronted with active complement, they were partially resistant to complement-mediated lysis. However, by removing CD55, CD59, and Factor H from the virus surface or inhibiting their biological functions, the researchers were able to restore complement-mediated clearance of SARS-CoV-2. This highlights the potential for targeted interventions to enhance the host’s immune response against the virus.
The leader of the study, Anna Ohradanova-Repic, explains that by hijacking these three proteins, SARS-CoV-2 can evade the complement system and reduce or delay viral clearance in the infected host. This evasion not only affects virus elimination but can also lead to significant inflammation, a key feature of both severe COVID-19 and Long COVID. First author Laura Gebetsberger emphasizes that uncovering immune evasion mechanisms that allow the virus to persist within the host for longer periods enhances our understanding of the acute and long-term impacts of SARS-CoV-2 infection.
Overall, this study provides important insights into how SARS-CoV-2 evades the host immune response by hijacking key host proteins involved in the complement system. Understanding these mechanisms is crucial for developing targeted interventions to enhance viral clearance and mitigate the inflammatory response associated with severe COVID-19 and Long COVID. By unraveling the immune evasion strategies of the virus, researchers can better understand the factors contributing to the persistence and severity of SARS-CoV-2 infections, ultimately leading to improved treatment strategies and outcomes for patients.