Endothelial cell permeability and adherens junction disruption induced by junín virus infection.
Junín virus (JUNV) is endemic to the fertile Pampas of Argentina, maintained in nature by the rodent host Calomys musculinus, and the causative agent of Argentine hemorrhagic fever (AHF), which is characterized by vascular dysfunction and fluid distribution abnormalities. Clinical as well as experimental studies implicate involvement of the endothelium in the pathogenesis of AHF, although little is known of its role. JUNV has been shown to result in productive infection of endothelial cells (ECs) in vitro with no visible cytopathic effects. In this study, we show that direct JUNV infection of primary human ECs results in increased vascular permeability as measured by electric cell substrate impedance sensing and transwell permeability assays. We also show that EC adherens junctions are disrupted during virus infection, which may provide insight into the role of the endothelium in the pathogenesis of AHF and possibly, other viral hemorrhagic fevers.
Departments of Pathology and Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas hmlander@utmb.edu.
Heather M
HM
Lander
Departments of Pathology and Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas.
Ashley M
AM
Grant
Departments of Pathology and Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas.
Thomas
T
Albrecht
Departments of Pathology and Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas.
Terence
T
Hill
Departments of Pathology and Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas.
Clarence J
CJ
Peters
D022005:Adherens Junctions / Q000821:virology*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D051177:Catenins / Q000378:metabolism; D002463:Cell Membrane Permeability; D018932:Chemokine CCL2 / Q000378:metabolism; D003911:Dextrans / Q000378:metabolism*; D004197:Disease Reservoirs; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives* / Q000378:metabolism; D006478:Hemorrhagic Fever, American / Q000821:virology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D018051:Junin virus / Q000502:physiology*; D010539:Permeability; D016205:Sigmodontinae / Q000821:virology*; D000095002:Delta Catenin; D000099152:Cadherin 5
D015703:Antigens, CD; D015820:Cadherins; D051177:Catenins; D018932:Chemokine CCL2; D003911:Dextrans; D016650:Fluorescein-5-isothiocyanate; D015850:Interleukin-6; D000095002:Delta Catenin; D000099152:Cadherin 5; C111835:CCL2 protein, human; C508600:IL6 protein, human; C015219:fluorescein isothiocyanate dextran