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A clinical isolate of dengue virus and its proteins induce apoptosis in HMEC-1 cells: a possible implication in pathogenesis

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Abstract

Cumulative studies have demonstrated that dengue virus infection results in the induction of apoptosis of certain cells in vitro. Moreover, apoptosis of microvascular endothelial cells in the brain and in the intestinal serosa has been demonstrated postmortem in dengue virus (DENV)-infected patients. In this work, human microvascular endothelial cells (HMEC-1) infected with a DENV-2 clinical isolate, or HMEC-1 cells transfected with its protease sequence (NS3pro) or its complex (NS2BNS3pro) were able to trigger apoptosis after 24 h of infection or transfection. The infected or transfected HMEC-1 cells displayed the distinctive apoptotic hallmarks, which include cytoplasmic shrinkage and plasma membrane blebbing. In addition, the transfected HMEC-1 cells showed biochemical changes such as exposure of phosphatidylserine on the outer leaflet of the plasma membrane, TUNEL positivity, caspase 3 activation and cleaved PARP, a central regulator of apoptosis. These findings suggest the role of such proteins from the clinical isolate in the induction of apoptosis.

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Acknowledgments

We are thankful to Fernando Medina for his assistance in C6/36 culture, and Julio García Cordero (185263) and Melina Vasquez Ochoa (158086), who received predoctoral fellowships from CONACYT. This work was supported by CONACYT (grant no. 40199) and by DENFRAME Consortium INCO 517711.

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Authors and Affiliations

  1. Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados, IPN Av. IPN 2508, 07360, Mexico DF, Mexico

    Melina Vásquez Ochoa, Julio García Cordero, Leopoldo Santos Argumedo, Nicolas Villegas Sepúlveda & Leticia Cedillo Barrón

  2. Laboratorio de Inmunología UMF de la FES Iztacala, Universidad Autónoma de México, Av. de los Barrios s/n Los Reyes Iztacala, Tlanepantla, Estado de México, Mexico

    Benito Gutiérrez Castañeda

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  1. Melina Vásquez Ochoa
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  2. Julio García Cordero
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  3. Benito Gutiérrez Castañeda
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  4. Leopoldo Santos Argumedo
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  5. Nicolas Villegas Sepúlveda
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  6. Leticia Cedillo Barrón
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Correspondence to Leticia Cedillo Barrón.

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Melina Vásquez Ochoa and Julio García Cordero contributed equally to this work.

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Vásquez Ochoa, M., García Cordero, J., Gutiérrez Castañeda, B. et al. A clinical isolate of dengue virus and its proteins induce apoptosis in HMEC-1 cells: a possible implication in pathogenesis. Arch Virol 154, 919–928 (2009). https://doi.org/10.1007/s00705-009-0396-7

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  • DOI: https://doi.org/10.1007/s00705-009-0396-7

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