| 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; Yang, YT; Lee, CH; Ho, LLT; Hsu, WM; Ku, HH; Chen, SJ; Chen, SSL; Chang, MDT; Wu, CW; Juan, LJ |
| Contributors: |
張大慈 |
| Publisher Information: |
American Association of Immunologists |
| Publication Year: |
2006 |
| Collection: |
National Tsing Hua University Institutional Repository (NTHUR) |
| Subject Terms: |
HCMV |
| Time: |
39 |
| Description: |
2050118010016 ; 生科系 ; 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: |
journal/newspaper |
| File Description: |
118 bytes; text/html |
| Language: |
English |
| ISSN: |
0022-1767 |
| Relation: |
JOURNAL OF IMMUNOLOGY,American Association of Immunologists,Volume 177,Issue 9,NOV 1 2006,Pages 6199-6206; http://nthur.lib.nthu.edu.tw/dspace/handle/987654321/48927 |
| Availability: |
http://nthur.lib.nthu.edu.tw/dspace/handle/987654321/48927 |
| Accession Number: |
edsbas.7067C785 |
| Database: |
BASE |