| Title: |
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 |
| Authors: |
Chiou; SH; Yang; YP; Lin; JC; Hsu; CH; Jhang; HC; YT; Lee; Ho; LLT; WM; Ku; HH; Chen; SJ; SSL; Chang; MDT; Wu; CW; Juan; LJ |
| Contributors: |
National Institute of Cancer Research |
| Publisher Information: |
AMER ASSOC IMMUNOLOGISTS |
| Publication Year: |
2006 |
| Collection: |
National Health Research Institutes (NHRI): Institutional Repository / 國家衛生研究院機構典藏 |
| Subject Terms: |
Immunology |
| Description: |
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 P13K and might also render cells resistant to TRAIL-mediated death. Finally, enhanced c-FLIP signals were immunohistochemically detected in FE-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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf; 683966 bytes |
| Language: |
English |
| Relation: |
Journal of Immunology. 2006 Nov;177(9):6199-6206.; http://ir.nhri.org.tw/handle/3990099045/2694; http://ir.nhri.org.tw/bitstream/3990099045/2694/1/000241477400053.pdf |
| Availability: |
http://ir.nhri.org.tw/handle/3990099045/2694; http://ir.nhri.org.tw/bitstream/3990099045/2694/1/000241477400053.pdf |
| Accession Number: |
edsbas.F9D6FAA2 |
| Database: |
BASE |