Chiou SH |
------>authors3_c= ------>paper_class1=1 ------>Impact_Factor=6.068 ------>paper_class3=2 ------>paper_class2=1 ------>vol=177 ------>confirm_bywho=None ------>insert_bywho=wmhsu ------>Jurnal_Rank=10.9 ------>authors4_c= ------>comm_author= ------>patent_EDate=None ------>authors5_c= ------>publish_day=1 ------>paper_class2Letter=None ------>page2=6206 ------>medlineContent= ------>unit=000 ------>insert_date=20081205 ------>iam=7 ------>update_date=None ------>author=??? ------>change_event=1 ------>ISSN= ------>authors_c= ------>score=461 ------>journal_name=Journal of Immunology ------>paper_name=The immediate early 2 protein of HCMV mediates the apoptotic control in HCMV retinitis through up-regulation of the cellular FLICE inhibitory protein expression ------>confirm_date=None ------>tch_id=096076 ------>pmid=17056549 ------>page1=6199 ------>fullAbstract=Human CMV (HCMV) is a widespread human pathogen that causes blindness by inducing retinitis in AIDS patients. Previously, we showed that viral immediate early 2 (IE2) protein may allow HCMV to evade the immune control by killing the Fas receptor-positive T lymphocytes attracted to the infected retina with increased secretion of Fas ligand (FasL). In this study, we further demonstrate that the secreted FasL also kills uninfected Fas-rich bystander retinal cells and that IE2 simultaneously protects the infected cells from undergoing apoptotic death, in part, by activating the expression of cellular FLIP (c-FLIP), an antiapoptotic molecule that blocks the direct downstream executer caspase 8 of the FasL/Fas pathway. c-FLIP induction requires the N-terminal 98 residues of IE2 and the c-FLIP promoter region spanning nucleotides -978 to -696. In vivo association of IE2 to this region, IE2-specific c-FLIP activation, and decrease of FasL-up-regulated activities of caspases 8 and 3 were all demonstrated in HCMV-infected human retinal cells. Moreover, c-FLIP up-regulation by IE2 appeared to involve PI3K and might also render cells resistant to TRAIL-mediated death. Finally, enhanced c-FLIP signals were immunohistochemically detected in IE-positive cells in the HCMV-infected lesions of the human retina. Taken together, these data demonstrate specific activation of c-FLIP by HCMV IE2 and indicate a novel role for c-FLIP in the pathogenesis of HCMV retinitis. ------>tmu_sno=None ------>sno=20537 ------>authors2=Yang YP ------>authors3=Lin JC ------>authors4=Hsu CH ------>authors5=Jhang HC ------>authors6=Ho LT, Hsu WM, Juan LJ ------>authors6_c= ------>authors=Chiou SH ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c= ------>publish_area=0 ------>updateTitle=The immediate early 2 protein of human cytomegalovirus (HCMV) mediates the apoptotic control in HCMV retinitis through up-regulation of the cellular FLICE-inhibitory protein expression. ------>language=2 ------>check_flag=None ------>submit_date=None ------>country=None ------>no= ------>patent_SDate=None ------>update_bywho=None ------>publish_year=2006 ------>submit_flag=None ------>publish_month=5 |