Complement Activation-Independent Attenuation of SARS-CoV-2 Infection by C1q and C4b-Binding Protein

Area of Science:

• Immunology
• Virology
• Molecular Biology

Background:

• The complement system is crucial for innate immunity against viruses.
• Severe SARS-CoV-2 infection involves exaggerated complement activation and cytokine storms.
• Complement proteins C1q and C4b-binding protein (C4BP) may have protective roles against viral infections.

Purpose of the Study:

• To investigate the complement activation-independent role of C1q and C4BP against SARS-CoV-2 infection.
• To examine the direct interactions of C1q and C4BP with SARS-CoV-2 spike protein and its receptor binding domain (RBD).
• To assess the effects of C1q and C4BP on SARS-CoV-2 cell entry and the associated immune response.

Main Methods:

• Direct ELISA to examine protein interactions.
• RT-qPCR to evaluate immune response modulation.
• Cell binding and viral entry assays using pseudotype particles.

Main Results:

• C1q and C4BP directly bind to SARS-CoV-2 pseudotype particles via the RBD of the spike protein.
• C1q and C4BP reduce viral binding and transduction into host cells.
• Treatment with C1q and C4BP decreases mRNA levels of pro-inflammatory cytokines and chemokines, including IL-1β, IL-8, IL-6, TNF-α, IFN-α, and RANTES.
• C1q and C4BP treatment reduces SARS-CoV-2 pseudotype infection-mediated NF-κB activation.

Conclusions:

• Locally produced C1q and C4BP provide protection against SARS-CoV-2 infection independently of complement activation.
• These proteins inhibit virus binding to host cells and attenuate the inflammatory response.
• C1q and C4BP represent potential therapeutic targets for managing SARS-CoV-2 infection.