Complement components regulates ferroptosis in CVB3 viral myocarditis by interatction with TFRC

Area of Science:

• Cardiology
• Virology
• Immunology

Background:

• Coxsackievirus B3 (CVB3) infection causes myocarditis characterized by dysregulated cell death and inflammation.
• Complement C4 and C3 are key components of the classical complement pathway involved in early viral infection responses.

Purpose of the Study:

• To investigate the role of ferroptosis and its regulators in CVB3-induced viral myocarditis.
• To explore the interaction between ferroptosis pathways and complement system components in the context of CVB3 infection.

Main Methods:

• A mouse model of CVB3 viral myocarditis was established using Fer-1 treatment.
• Co-immunoprecipitation and mass spectrometry were employed to identify interactions with transferrin receptor (TFRC).
• Functional experiments were conducted to validate the role of complement components in ferroptosis regulation.

Main Results:

• The ferroptosis inhibitor Fer-1 reduced inflammation and ferroptosis in CVB3 myocarditis.
• Transferrin receptor (TFRC) was identified as a key factor interacting with complement C4, influencing C4b and C3 levels.
• Fer-1 treatment prevented C3 consumption and C4b overload during CVB3 infection.

Conclusions:

• Ferroptosis in viral myocarditis involves crosstalk with complement C4 via TFRC.
• Modulating the complement C4/C3 pathway shows potential for rescuing ferroptosis in CVB3-infected cardiomyocytes.