SARS-CoV-2 Outwits Immune System, Prolonging Infection

SARS-CoV-2 inhibits the function of the complement system, a crucial element of early antiviral immunity, by hijacking three crucial host proteins, according to research from the Medical Universities of Vienna and Innsbruck.

This seriously hinders viral clearance, which could have an impact on the progression of acute COVID-19 infections as well as the aftermath of COVID-19. The study was published in the journal Emerging Microbes & Infections.

For viral infections to be resolved and post-infectious consequences to be avoided, an early and efficient immune response is essential. A key component of antiviral immunity, the complement system is a series of proteins that are present in the bloodstream and at mucosal locations like the respiratory tract.

Complement, which is activated via three distinct pathways, directly causes the destruction (lysis) of viral particles, facilitating their removal. A group of host molecules known as complement regulatory proteins quickly deactivate complement to stop bystander damage to host cells.

SARS-CoV-2 successfully protects itself from complement-mediated lysis by hijacking three of these regulatory proteins, CD55, CD59, and Factor H, according to a new study conducted by Anna Ohradanova-Repic and colleagues from the Center for Pathophysiology, Infectiology, and Immunology at the Medical University of Vienna in cooperation with the team of Heribert Stoiber from the Institute of Virology at the Medical University of Innsbruck.

Hijacking Host Proteins for Effective Complement Resistance

Researchers found that when SARS-CoV-2 is propagated in human cells, the virus particles pick up the cellular proteins CD55 and CD59. SARS-CoV-2 also binds to Factor H, another complement regulating protein that is mostly present in the bloodstream, according to another research.

The virus particles were shown to be somewhat resistant to complement-mediated lysis when they were exposed to active complement. Inhibiting the biological activity of CD55, CD59, and Factor H or removing them from the virus surface allowed the researchers to 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, Study Lead, Medical University of Vienna 

In addition to affecting virus elimination, complement's complex relationship with other immune system components can result in substantial inflammation, which is a hallmark 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.”

Laura Gebetsberger, Study First Author, Medical University of Vienna