title: Dengue virus infection of SK Hep1 cells: inhibition of in vitro angiogenesis and altered cytomorphology by expressed viral envelope glycoprotein.
abstract: Dengue virus (DENV) infection of human endothelial cells has been implicated in the pathobiology of dengue hemorrhagic fever and dengue shock syndrome. However, the mechanisms by which DENV infections alter the functional physiology of endothelial cells remain incompletely understood. In the present study, we examined the susceptibility of a human liver sinusoidal endothelial cell line SK Hep1 to all four serotypes of DENV and studied the effect of the virus on in vitro angiogenesis. All four serotypes of DENV could infect the SK Hep1 cells, but showed variable cytopathic effects, the most pronounced being that of DENV-2. Electron microscopy of the infected cells showed significant ultrastructural changes. In vitro angiogenesis assays on DENV-2 exposed SK Hep1 cells in the matrigel system showed inhibition compared with the controls. Importantly, transfection and transient expression of the DENV-2 envelope glycoprotein (E) in these cells showed drastic alterations in cell shapes and the E protein could be localized by fluorescence microscopy in terminal knob-like structures. Therefore, SK Hep1, a human hepatic sinusoid-derived endothelial cell line, may constitute a potential model to study DENV-endothelial cell interactions in vitro, especially towards understanding the possible virus-induced changes in hepatic endothelium and its role in disease pathogenesis.
authors.affiliation: National Institute of Virology, Pune, India National Institute of Immunohaematology, KEM Hospital, Mumbai, India.
authors.forename: Atanu
authors.initials: A
authors.lastname: Basu
authors.forename: Preksha
authors.initials: P
authors.lastname: Jain
authors.forename: Payel
authors.initials: P
authors.lastname: Sarkar
authors.forename: Shobha
authors.initials: S
authors.lastname: Gangodkar
authors.forename: Divija
authors.initials: D
authors.lastname: Deshpande
authors.forename: Ketaki
authors.initials: K
authors.lastname: Ganti
authors.forename: Shrimati
authors.initials: S
authors.lastname: Shetty
authors.forename: Kanjaksha
authors.initials: K
authors.lastname: Ghosh
mesh_terms: D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D003716:Dengue Virus / Q000472:pathogenicity*; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology* / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D046529:Microscopy, Electron, Transmission; D018919:Neovascularization, Physiologic; D009924:Organ Culture Techniques; D014759:Viral Envelope Proteins / Q000378:metabolism*
chemical_list: C051821:E-glycoprotein, Dengue virus type 2; D014759:Viral Envelope Proteins