Published Online
on July 12, 2004

A more recent version of this article appeared on December 7, 2004

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Submitted on March 18, 2004
Revised on June 4, 2004
Accepted on June 4, 2004

Protective Role for Interferon- in Coxsackievirus B3 Infection

Raj Deonarain PhD, Dante Cerullo MSc, Koichi Fuse MD, PhD, Peter P. Liu MD, and 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.

^* To whom correspondence should be addressed. E-mail: en.fish{at}utoronto.ca.

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 - 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- in protection from coxsackievirus B3 (CVB3) infection, mice lacking the IFN- gene were infected with 10³ plaque-forming units of CVB3. In contrast to wild-type mice that exhibit an intact IFN- 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-^-/- mice.

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

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

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