Highly pathogenic coronavirus N protein aggravates inflammation by MASP-2-mediated lectin complement pathway...

Area of Science:

• Immunology
• Virology
• Molecular Biology

Background:

• Excessive inflammation is key in severe human coronavirus infections.
• The precise mechanisms driving this pathogenesis remain incompletely understood.

Purpose of the Study:

• To investigate the role of coronavirus N proteins in complement activation.
• To explore potential therapeutic strategies targeting complement pathways for severe coronavirus disease.

Main Methods:

• Investigated the interaction between N proteins (SARS-CoV, MERS-CoV, SARS-CoV-2) and MASP-2.
• Assessed complement activation markers (MASP-2, C4b, C3, C5b-9) in vitro and in vivo.
• Evaluated the impact of blocking N protein:MASP-2 interaction or complement suppression on lung injury in a mouse model.

Main Results:

• Coronavirus N proteins bind to MASP-2, a key enzyme in the lectin complement pathway.
• This interaction potentiates MBL-dependent MASP-2 activation, leading to excessive complement cascade and deposition.
• N protein expression induced lung injury in mice, which was ameliorated by inhibiting complement activation.
• Complement hyperactivation was observed in patients with SARS-CoV-2 infection.

Conclusions:

• Coronavirus N proteins trigger excessive complement activation via MASP-2.
• Targeting the N protein:MASP-2 interaction or downstream complement components may mitigate coronavirus-induced lung injury.
• Complement suppression presents a promising therapeutic avenue for severe coronavirus pneumonia.