The Neuraminidase Inhibitor Peramivir Ameliorates Myocarditis Induced by Influenza A (H1n1pdm) Virus in a Murine Model

Abstract

Severe influenza sometimes causes myocarditis. To analyze the effects of peramivir on influenza A (H1N1pdm) virus myocarditis, we investigated survival rates, cardiac function, histological findings and cytokine induction in murine influenza A (H1N1pdm) virus-induced myocarditis. Eight-week-old BALB/c male mice were infected intranasally with influenza A (H1N1pdm) virus, and then divided into 2 groups: control group, which was injected with saline; and peramivir-treatment group, which was treated with peramivir. Histological studies, echocardiograms and quantitative analysis of viral RNA and mRNA for inflammatory cytokines and adhesion molecules were performed. Treatment with peramivir led to a significant improvement in survival (p<0.01 vs. control group). Fractional shortening (FS) of peramivir-treatment group (44.7%, p<0.01) was significantly higher than that of control group (27.7%) on day 8. Histological examinations revealed localized myocarditis with lymphocyte infiltration, and myocarditis lesions were found in perivascular areas or associated with pericarditis; treatment with peramivir improved these findings. Quantity of influenza virus genome in heart and lung tissues was suppressed in peramivirtreatment group. The expression of cytokine and adhesion molecule mRNA was suppressed in peramivir-treatment group. Peramivir improved influenza A (H1N1pdm) virus-induced myocarditis.