Influenza virus replication in cardiomyocytes drives heart dysfunction and fibrosis

Area of Science:

• Virology
• Cardiology
• Immunology

Background:

• Influenza virus infection can lead to cardiac dysfunction.
• The exact mechanism causing influenza-associated cardiac pathology, whether direct cardiac viral infection or systemic inflammation from lung infection, is not fully understood.

Purpose of the Study:

• To investigate the role of direct cardiac viral replication in influenza-associated cardiac pathology.
• To differentiate between direct cardiac infection and systemic lung inflammation as causes of heart dysfunction during influenza.

Main Methods:

• Generated a novel heart-attenuated influenza virus by incorporating miRNA target sequences into the viral genome.
• Infected mice with the modified virus and a control virus, assessing viral titers in the heart and lungs.
• Evaluated cardiac function, conduction irregularities, and fibrosis, particularly in a mouse model lacking interferon-induced transmembrane protein 3 (IFITM3).

Main Results:

• The heart-attenuated virus showed significantly reduced viral titers in the heart but replicated fully in the lungs.
• Systemic inflammation and weight loss were similar between mice infected with the attenuated and control viruses.
• The attenuated virus led to fewer cardiac conduction irregularities and significantly less cardiac fibrosis in IFITM3-deficient mice.

Conclusions:

• Robust influenza virus replication within cardiac tissue is a critical factor for developing cardiac pathology.
• Direct cardiac infection, rather than solely systemic inflammation originating from lung infection, drives influenza-associated cardiac dysfunction.
• Targeting cardiac viral replication may be a strategy to mitigate heart complications during severe influenza infections.