Medici M Antonietta, Sciortino M Teresa, Perri Donata, Amici Carla, Avitabile Elisa, Ciotti Marco, Balestrieri Emanuela, De Smaele Enrico, Franzoso Guido, Mastino Antonio
Department of Microbiological, Genetic and Molecular Sciences, Salita Sperone 31, University of Messina, 98166 Messina, Italy.
J Biol Chem. 2003 Sep 19;278(38):36059-67. doi: 10.1074/jbc.M306198200. Epub 2003 Jul 4.
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.
研究了单纯疱疹病毒1型（HSV-1）在抗细胞凋亡过程中涉及的信号。以U937单核细胞样细胞作为实验模型，我们证明HSV-1在感染后能迅速使这些细胞对Fas诱导的细胞凋亡产生抗性。紫外线灭活的病毒以及HSV-1的包膜糖蛋白D（gD）本身对Fas诱导的细胞凋亡具有保护作用。gD可激活核因子κB（NF-κB），在稳定转染显性负性突变体I-κBα的细胞中，gD对Fas介导的细胞凋亡的保护作用被消除，这表明在我们的实验模型中，NF-κB的激活在gD的抗凋亡活性中发挥作用。此外，NF-κB依赖性的对Fas介导的细胞凋亡的保护作用与半胱天冬酶-8活性水平降低以及细胞内抗凋亡蛋白的上调有关。
