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J. Biol. Chem., Vol. 278, Issue 38, 36059-36067, September 19, 2003

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Protection by Herpes Simplex Virus Glycoprotein D against Fas-mediated Apoptosis

ROLE OF NUCLEAR FACTOR B^*

M. Antonietta Medici , M. Teresa Sciortino , Donata Perri , Carla Amici , Elisa Avitabile ¶, Marco Ciotti ||, Emanuela Balestrieri , Enrico De Smaele **, Guido Franzoso ** and Antonio Mastino  

From the Department of Microbiological, Genetic and Molecular Sciences, Salita Sperone 31, University of Messina, 98166 Messina, Italy, the Department of Biology, University of Rome "Tor Vergata," 00133 Rome, Italy, the ^¶Department of Experimental Pathology, Section of Microbiology and Virology, University of Bologna, 40126 Bologna, Italy, the ^||Department of Experimental Medicine and Biochemical Sciences, "Tor Vergata" University Hospital, University of Rome "Tor Vergata," 00133 Rome, Italy, and the ^**Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, Illinois 60637

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-B was activated by gD, and protection against Fas-mediated apoptosis by gD was abolished in cells stably transfected with a dominant negative mutant I-B, indicating that NF-B activation plays a role in the antiapoptotic activity of gD in our experimental model. Moreover, NF-B-dependent protection against Fas-mediated apoptosis was associated with decreased levels of caspase-8 activity and with the up-regulation of intracellular antiapoptotic proteins.

Received for publication, June 12, 2003

^* This work was supported by grants from the Italian Ministry of Education, University and Research, Research Projects of National Interest, from the Consiglio Nazionale delle Ricerche Special Project "Biogerontology," and from the University of Messina. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed. Tel.: 39090-393481; Fax: 3990-392733; E-mail: mastino{at}med.uniroma2.it.

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