Dengue Virus neither Directly Mediates Hyperpermeability nor Enhances Tumor Necrosis Factor-α-Induced Permeability In Vitro

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  • Raekiansyah Muhareva
    Department of Virology, Institute of Tropical Medicine, Nagasaki University and GCOE Program
  • Espada-Murao Lyre Anni
    Department of Virology, Institute of Tropical Medicine, Nagasaki University and GCOE Program
  • Okamoto Kenta
    Department of Virology, Institute of Tropical Medicine, Nagasaki University and GCOE Program
  • Kubo Toru
    Department of Virology, Institute of Tropical Medicine, Nagasaki University and GCOE Program
  • Morita Kouichi
    Department of Virology, Institute of Tropical Medicine, Nagasaki University and GCOE Program

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  • Dengue Virus neither Directly Mediates Hyperpermeability nor Enhances Tumor Necrosis Factor-^|^alpha;-Induced Permeability In Vitro

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Abstract

The mechanisms of endothelial barrier dysfunction in dengue disease remain poorly understood. Endothelial cell (EC) death due to virus infection or in combination with an infection-induced cytokine storm is deemed as one of the major causes of plasma leakage. Using an in vitro model of human endothelia and several dengue virus (DENV) strains (including a clinical isolate), the direct consequence of infection on endothelial permeability was investigated throughout the course of the infection. All employed DENV-2 strains were able to infect and replicate in ECs. Rather than increase endothelial permeability, DENV infection alone enhanced cell barrier integrity up to 7 days postinfection. Improved cell barrier function was mediated by type I interferon activation at the early phase of infection and by the survival advantage of the infected cells at the late phase of infection. Consistent with this phenomenon, DENV infection did not augment tumor necrosis factor-α-induced permeability. Our results prove that DENV infection does not directly account for vascular permeability; DENV neither induces hyperpermeability nor exacerbates the permeabilizing effect of cytokines. The contributory role of other factors on plasma leakage during dengue disease warrants further investigation.

Journal

  • Japanese Journal of Infectious Diseases

    Japanese Journal of Infectious Diseases 67 (2), 86-94, 2014

    National Institute of Infectious Diseases, Japanese Journal of Infectious Diseases Editorial Committee

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