Differential modulation of SARS-CoV-2 infection by complement factor H and properdin.

Area of Science:

• Immunology
• Virology
• Complement System

Background:

• Severe SARS-CoV-2 infection is characterized by immune dysregulation and excessive inflammation.
• The complement system, particularly the alternative pathway, plays a critical role in COVID-19 immunopathology.
• Decreased Factor H (FH) and elevated properdin (FP) levels are observed in severe SARS-CoV-2 infection.

Purpose of the Study:

• To investigate the potential immune-protective roles of FH and FP against SARS-CoV-2 infection.
• To evaluate the effects of FH and FP on SARS-CoV-2 interaction with host cells.
• To assess the immunomodulatory roles of FH and FP in SARS-CoV-2-induced cytokine responses.

Main Methods:

• Direct ELISA to assess binding of FH and FP to SARS-CoV-2 spike (S) and receptor binding domain (RBD).
• Cell binding and viral entry assays using lentiviral pseudotypes to evaluate modulatory effects of FH, FP, and TSR4+5.
• RT-qPCR to assess immunomodulatory roles of FH and FP in cytokine responses.

Main Results:

• FH and FP bind to SARS-CoV-2 S and RBD proteins.
• FP and TSR4+5 enhanced SARS-CoV-2 pseudotype cell binding and entry, increasing pro-inflammatory cytokines.
• FH treatment decreased SARS-CoV-2 pseudotype cell binding and entry, downregulating pro-inflammatory cytokines.

Conclusions:

• FH may act as an inhibitor of SARS-CoV-2 cell entry and binding, reducing inflammation independently of complement activation.
• FP may facilitate viral entry and binding, potentially exacerbating hyperinflammation and disease severity.
• Understanding FH and FP roles could inform therapeutic strategies for severe COVID-19.