Volume 88, Issue 1
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Dengue hemorrhagic fever is characterized by a unique vascular leakage syndrome. The mechanisms of endothelial barrier dysfunction in dengue hemorrhagic fever are not well understood. We examined the modulation of endothelial barrier function in dengue virus type 2 (DENV2) infections using primary human umbilical vein endothelial cells. We demonstrated that the increase in endothelial barrier function within 72 hours after DENV2 infection is mediated by type I interferon–dependent CD73 up-regulation. After 72 hours, DENV2 slowed the recovery of endothelial barrier function in response to tumor necrosis factor-α or vascular endothelial growth factor. This phenomenon was likely caused by type I interferon receptor signaling inhibition and lower CD73 levels in DENV2-infected endothelial cells. Our findings suggest that during DENV2 infection, endothelial barrier homeostasis is maintained by a balance between pro-inflammatory and pro-angiogenic cytokines, and type I interferon–dependent CD73 expression and activity.

[open-access] This is an Open Access article distributed under the terms of the American Society of Tropical Medicine and Hygiene's Re-use License which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


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  • Received : 03 Aug 2012
  • Accepted : 30 Sep 2012

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