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(Circulation. 2004;110:3540-3543.)
© 2004 American Heart Association, Inc.

Heart Failure

Protective Role for Interferon-ß in Coxsackievirus B3 Infection

Raj Deonarain, PhD; Dante Cerullo, MSc; Koichi Fuse, MD, PhD; Peter P. Liu, MD; Eleanor N. Fish, PhD

From the Toronto General Research Institute (R.D., P.P.L., E.N.F.) and Heart & Stroke/Richard Lewar Centre of Excellence, University of Toronto (D.C., K.F., P.P.L.), Toronto, Ontario, Canada.

Correspondence to Eleanor N. Fish, Toronto General Research Institute, University Health Network, 67 College St, Room 424, Toronto, Ontario M5G 2M1 Canada. E-mail en.fish{at}utoronto.ca

Received March 18, 2004; de novo received May 5, 2004; revision received June 4, 2004; accepted June 4, 2004.

Background— Coxsackievirus-induced myocarditis can be a serious cause of heart failure. In the absence of a specific antiviral therapy, modulating the host immune response may be protective. Interferons (IFNs)- and -ß perform a fundamental role in innate and adaptive antiviral responses, thereby presenting as candidate therapeutics for coxsackievirus infections.

Methods and Results— To examine the contribution of IFN-ß in protection from coxsackievirus B3 (CVB3) infection, mice lacking the IFN-ß gene were infected with 10³ plaque-forming units of CVB3. In contrast to wild-type mice that exhibit an intact IFN-ß response, we observed increased susceptibility to infection (70% mortality), a downregulation of IFN-stimulated gene targets (2'-5' oligoadenylate synthetase, serine/threonine protein kinase, the GTPase Mx), and cardiomyocyte breakdown and disruption in the IFN-ß^–/– mice.

Conclusions— Viewed together, these results clearly demonstrate that IFN-ß is important in mediating protection against CVB3-induced myocarditis.

Key Words: interferon beta • coxsackievirus • interferon-stimulated genes

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