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

Antivir Ther. 2011;16(4):577-84. doi: 10.3851/IMP1752.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • Carrier Proteins / genetics
  • Cell Cycle Proteins
  • Cells, Cultured
  • Coxsackievirus Infections / drug therapy*
  • Coxsackievirus Infections / virology
  • Enterovirus B, Human / drug effects
  • Eukaryotic Initiation Factors
  • Fibroblasts / virology
  • HeLa Cells
  • Humans
  • Interferon-beta / pharmacology
  • Interferon-beta / therapeutic use
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myocarditis / drug therapy
  • Myocarditis / virology
  • Phosphoproteins / deficiency
  • Phosphoproteins / genetics


  • Adaptor Proteins, Signal Transducing
  • Antiviral Agents
  • Carrier Proteins
  • Cell Cycle Proteins
  • Eif4ebp1 protein, mouse
  • Eukaryotic Initiation Factors
  • Phosphoproteins
  • Interferon-beta