A clinical isolate of dengue virus and its proteins induce apoptosis in HMEC-1 cells: a possible implication in pathogenesis.
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.
Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados, IPN Av. IPN 2508, 07360, Mexico DF, Mexico.
Melina
M
Vásquez Ochoa
Julio
J
García Cordero
Benito
B
Gutiérrez Castañeda
Leopoldo
L
Santos Argumedo
Nicolas
N
Villegas Sepúlveda
Leticia
L
Cedillo Barrón
D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry / Q000648:ultrastructure; D024161:Collagen Type XI / Q000378:metabolism; D003716:Dengue Virus / Q000472:pathogenicity*; D042783:Endothelial Cells / Q000821:virology; D006801:Humans; D020287:In Situ Nick-End Labeling; D010718:Phosphatidylserines / Q000032:analysis; D014161:Transduction, Genetic; D014162:Transfection; D014764:Viral Proteins / Q000633:toxicity*
C499319:COL11A2 protein, human; D024161:Collagen Type XI; D010718:Phosphatidylserines; D014764:Viral Proteins; D053148:Caspase 3