Antiviral effects of interferon-β are enhanced in the absence of the translational suppressor 4E-BP1 in myocarditis induced by Coxsackievirus B3

J. Daniel Burke, Nahum Sonenberg, Leonidas C. Platanias, Eleanor N. Fish

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Background: Viral myocarditis is most frequently associated with infection by Coxsackievirus B3 (CVB3). Interferon (IFN)-β therapy has been studied and could reduce virally induced tissue damage and improve heart function. Methods: In the present study we have investigated the role of translational suppression in the context of an IFN-α/β-mediated antiviral immune response to CVB3 infection. Specifically, we examined the effects of IFN-α/β treatment of CVB3-infected mouse embryonic fibroblast cells and splenocytes lacking eukaryotic initiation factor 4E binding protein-1 (4E-BP1), a suppressor of 5′-capped mRNA translation. Extending these in vitro studies, we examined the effects of CVB3 infection and IFN-β treatment in 4E-BP1-/- mice. Results: Our data show that 4E-BP1 -/- cells are more sensitive to the antiviral effects of IFN-α4 and IFN-β treatment than 4E-BP1+/+ cells when infected with CVB3. Similarly, 4E-BP1-/- mice are more sensitive to treatment with IFN-β, exhibiting lower viral titres in heart tissue than 4E-BP1 +/+ mice during the course of infection. Additionally, we demonstrate that treatment with IFN-β reduces inflammatory infiltrates into the hearts of infected mice. Conclusions: These data identify 4E-BP1 as a novel drug target to augment responsiveness to IFN-β therapy in CVB3-induced myocarditis.

Original languageEnglish (US)
Pages (from-to)577-584
Number of pages8
JournalAntiviral Therapy
Volume16
Issue number4
DOIs
StatePublished - 2011

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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