Aberrant PD-1 ligand expression contributes to the myocardial inflammatory injury caused by Coxsackievirus B infection

Area of Science:

• Virology
• Immunology
• Cardiology

Background:

• Coxsackievirus group B (CVB) is a primary cause of human viral myocarditis.
• CVB-induced myocarditis involves persistent viral infection and immune-driven inflammation.
• Costimulatory signals are essential for adaptive immune responses.

Purpose of the Study:

• To investigate how Coxsackievirus type 3 (CVB3) infection affects costimulatory molecule expression.
• To explore the role of PD-1 pathway in CVB3-induced myocarditis.
• To evaluate PD-L1 treatment as a potential therapy for viral myocarditis.

Main Methods:

• Analysis of costimulatory molecule expression profiles in CVB3-infected host cells.
• Investigating the mechanism of PD-1 ligand downregulation involving viral protease 3Cpro and AUF1.
• Assessing the therapeutic effect of systemic PD-L1 treatment on myocardial inflammation.

Main Results:

• CVB3 infection altered costimulatory molecule expression, notably decreasing PD-1 ligand.
• Viral protease 3Cpro cleaved AUF1, contributing to reduced PD-1 ligand expression and exacerbated myocardial injury.
• Systemic PD-L1 treatment promoted lymphocyte apoptosis and alleviated myocardial inflammation.

Conclusions:

• CVB3 infection impairs immune regulation through decreased PD-1 ligand expression.
• The PD-1 pathway represents a promising immunotherapeutic target for Coxsackievirus B-induced myocarditis.