Coxsackieviral replication and pathogenicity: lessons from gene modified animal models

Area of Science:

• Virology
• Cardiology
• Immunology

Background:

• Coxsackieviruses are linked to human myocarditis and dilated cardiomyopathy.
• Animal models, especially gene-targeted mice, are vital for understanding viral heart disease.
• Viral persistence and host immune responses are key factors in pathogenesis.

Purpose of the Study:

• To review cell culture and transgenic animal models of coxsackieviral persistence.
• To investigate the link between persistent viral genomes and cardiac pathology.
• To elucidate the role of innate immunity, specifically interferon signaling, in coxsackieviral infection.

Main Methods:

• Utilized cell culture models to study coxsackieviral persistence.
• Employed transgenic mice to mimic viral persistence and cardiac effects.
• Examined gene-targeted mice deficient in type I or type II interferon signaling.

Main Results:

• Low levels of persistent, replication-restricted coxsackieviral genomes induced a cytopathic effect in cardiac myocytes.
• A transgenic mouse model exhibited a phenotype closely resembling human dilated cardiomyopathy.
• Type I interferons, but not type II, were essential for controlling early viral replication and survival.

Conclusions:

• Persistent coxsackieviral genomes, even at low levels, can lead to dilated cardiomyopathy.
• Transgenic mouse models effectively replicate key features of human dilated cardiomyopathy.
• Type I interferon signaling is critical for host defense against coxsackieviral infections.