Coxsackie B viruses use multiple receptors to infect human cardiac cells

George Orthopoulos1, Kathy Triantafilou, Martha Triantafilou

  • 1University of Sussex, Infection and Immunity Group, School of Life Sciences, Falmer, Brighton, United Kingdom.

Insights

Viral myocarditis is a fatal heart inflammation. This study found that antibodies targeting known receptors (CAR and CD55) did not fully block Coxsackievirus B3 and B5 infection, suggesting new viral binding mechanisms.

Area of Science:

  • Cardiology
  • Virology
  • Molecular Biology

Background:

  • Viral myocarditis is a severe heart muscle inflammation, often fatal, primarily caused by human enteroviruses like Coxsackievirus B3 and B5.
  • Understanding viral entry mechanisms into cardiac cells is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the role of known receptors (Coxsackievirus adenovirus receptor protein - CAR and CD55) in Coxsackievirus B3 and B5 infection of cardiac cells.
  • To identify potential new receptors used by these viruses for cardiac muscle entry.

Main Methods:

  • Cardiac cells were treated with antibodies specific to CAR and CD55 to inhibit viral binding.
  • Viral infectivity and binding assays were performed to assess the efficacy of antibody-mediated inhibition.
  • Proteomic analysis was employed to identify novel viral binding proteins.

Main Results:

  • Antibodies against CAR and CD55 did not completely inhibit Coxsackievirus B3 and B5 binding or infectivity in cardiac cells.
  • Five novel proteins involved in Coxsackievirus binding to cardiac tissue were identified.
  • These newly identified proteins are distinct from CAR and CD55.

Conclusions:

  • The findings suggest that Coxsackievirus B3 and B5 may utilize a broader range of receptors than previously known for cardiac muscle infection.
  • Existing therapeutic strategies targeting CAR and CD55 may be insufficient to fully prevent viral myocarditis.
  • Further research into these novel receptors is warranted to understand their role in viral pathogenesis and develop targeted therapies.

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