Protection by herpes simplex virus glycoprotein D against Fas-mediated apoptosis: role of nuclear factor kappaB.
Signals involved in protection against apoptosis by herpes simplex virus 1 (HSV-1) were investigated. Using U937 monocytoid cells as an experimental model, we have demonstrated that HSV-1 rendered these cells resistant to Fas-induced apoptosis promptly after infection. UV-inactivated virus as well as the envelope glycoprotein D (gD) of HSV-1, by itself, exerted a protective effect on Fas-induced apoptosis. NF-kappaB was activated by gD, and protection against Fas-mediated apoptosis by gD was abolished in cells stably transfected with a dominant negative mutant I-kappaBalpha, indicating that NF-kappaB activation plays a role in the antiapoptotic activity of gD in our experimental model. Moreover, NF-kappaB-dependent protection against Fas-mediated apoptosis was associated with decreased levels of caspase-8 activity and with the up-regulation of intracellular antiapoptotic proteins.
Medici
M Antonietta
MA
Department of Microbiological, Genetic and Molecular Sciences, Salita Sperone 31, University of Messina, 98166 Messina, Italy.
Sciortino
M Teresa
MT
Perri
Donata
D
Amici
Carla
C
Avitabile
Elisa
E
Ciotti
Marco
M
Balestrieri
Emanuela
E
De Smaele
Enrico
E
Franzoso
Guido
G
Mastino
Antonio
A
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005799:Genes, Dominant; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D007700:Kinetics; D051379:Mice; D009154:Mutation; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors; D014162:Transfection; D020298:U937 Cells; D014466:Ultraviolet Rays; D015854:Up-Regulation; D014759:Viral Envelope Proteins / Q000378:metabolism / Q000502:physiology*; D019014:fas Receptor / Q000378:metabolism*
D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D014759:Viral Envelope Proteins; D019014:fas Receptor; C039447:glycoprotein D, Human herpesvirus 1; D000072000:NF-KappaB Inhibitor alpha; C505530:CASP8 protein, human; C506433:CASP9 protein, human; C505526:Casp8 protein, mouse; C506434:Casp9 protein, mouse; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases