title: Herpes simplex virus blocks Fas-mediated apoptosis independent of viral activation of NF-kappaB in human epithelial HEp-2 cells.
abstract: The goal of our study was to characterize the apoptotic response of herpes simplex virus (HSV)-infected, human epithelial HEp-2 cells to extrinsic treatments through the Fas receptor. Initially, we defined the Fas response of these cells. We found the following: (1) Treatment of HEp-2 cells with anti-Fas antibody or Fas ligand (FasL) alone did not induce apoptosis. (2) In addition, these inducers did not activate NF-kappaB in these cells. (3) The addition of cycloheximide (CHX) during these treatments caused a dramatic increase in programmed cell death. (4) HEp-2 cells infected with HSV for 6 h prior to anti-Fas plus CHX treatment were nonapoptotic, and (5) these cells possessed nuclear NFkappaB. (6) HSV blocked anti-Fas or FasL plus CHX-induced apoptosis in HEp-2 cells that stably expressed a dominant-negative form of IkappaBalpha. These results indicate that HSV infection can block the process of Fas-mediated apoptosis through a mechanism that is independent of viral activation of NFkappaB. Our findings help define the molecular mechanisms involved in HSV evasion of the cytokine-driven, innate immune response in human epithelial cells.
authors.affiliation: Department of Microbiology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA.
authors.forename: Elise R
authors.initials: ER
authors.lastname: Morton
authors.forename: John A
authors.initials: JA
authors.lastname: Blaho
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism / Q000502:physiology / Q000821:virology; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology; D008856:Microscopy, Fluorescence; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D018139:Simplexvirus / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D014775:Virus Activation; D019014:fas Receptor / Q000276:immunology / Q000502:physiology*
chemical_list: D016328:NF-kappa B; D011500:Protein Synthesis Inhibitors; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D003513:Cycloheximide