(Circulation. 2001;103:756.)
© 2001 American Heart Association, Inc.
Basic Science Reports |
Cardioselective Infection With Coxsackievirus B3 Requires Intact Type I Interferon Signaling
Implications for Mortality and Early Viral Replication
From Deutsches Herzzentrum and 1 Medizinische Klinik (R.W.), Technische Universität, Munich, Germany; the Department of Molecular Pathology (K.K., R.K.), University Hospital Tübingen, Tübingen, Germany; and the Department of Medicine (K.U.K.), University of California, San Diego.
Correspondence to Kirk U. Knowlton, MD, University of California at San Diego, Department of Medicine, 9500 Gilman Dr, La Jolla, CA 92093. E-mail kknowlton{at}ucsd.edu
Background—Interferons (IFNs) play an important role in antiviral defense and have therapeutic potential in coxsackievirus heart disease. However, little is known about the relative contributions of type I and type II IFN signaling in coxsackievirus B3 (CVB3) infection or their role in the cardioselective nature of CVB3 infection.
Methods and Results—Wild-type mice and mice deficient for either the type I or the type II IFN receptor (IFNR) were infected with CVB3. Infection of the type I IFNR–deficient mice with >103 plaque-forming units (pfu) of CVB3 resulted in 100% mortality within 2 to 4 days after infection. Death was rare in wild-type and type II IFNR–deficient mice after inoculation with as much as 108 pfu of CVB3. Surprisingly, the early mortality in the type I IFNR–deficient mice was not accompanied by higher virus titers in the heart. Unexpectedly, a dramatic increase of viral RNA in the liver was found to correlate with early mortality in type I IFNR–deficient mice.
Conclusions—Type I but not type II IFN signaling is essential for the prevention of early death due to CVB3 infection. Interestingly, neither type I or type II IFN signaling has a dramatic effect on early viral replication in the heart. However, lethal viral replication in the liver is controlled by type I IFNs. These results demonstrate that the IFN system is capable of modulating both viral pathogenicity and tissue tropism.
Key Words: cardiomyopathy • myocarditis • immune system • infection
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