Up-regulation of Fas ligand expression by human cytomegalovirus immediate-early gene product 2

A novel mechanism in cytomegalovirus-induced apoptosis in human retina

S. H. Chiou, J. H. Liu, Wen-Ming Hsu, S. S L Chen, S. Y. Chang, L. J. Juan, J. C. Lin, Y. T. Yang, W. W. Wong, C. Y. Liu, Y. S. Lin, W. T. Liu, C. W. Wu

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Human CMV (HCMV) is an important pathogen that causes widespread diseases in immunocompromised individuals. Among the opportunistic HCMV infections, HCMV retinitis is most common in transplant recipients and AIDS patients. It often leads to blindness if left untreated. The question as to how HCMV infection causes retinal pathogenesis remains unresolved. Here, we report that viral immediate-early gene product 2 (IE2), but not IE1, up-regulates the Fas ligand (FasL) expression in HCMVinfected human retinal pigment epithelium cells. Increased secretion of FasL from virally infected cells into cultured medium was observed upon HCMV infection. The capability of such cell-free medium to induce apoptosis of Fas (CD95)-expressing Jurkat cells further implies that Fas-FasL interaction might mediate cell death in the lesion of HCMV retinitis. To support this idea, we observed augmented soluble FasL levels in vitreous from AIDS patients with HCMV retinitis as compared with that from AIDS patients without HCMV infection. In addition, by in situ hybridization and immunohistochemistry, we detected enhanced signals of FasL, the existence of viral IE Ags and apoptotic cells at the same sites in the lesion of HCMV-infected retina. These results strongly suggest that IE2 induction of FasL expression in human retina might be an important event that takes place in the early stage of infection and finally leads to visual loss in individuals affiliated with HCMV retinitis.

Original languageEnglish
Pages (from-to)4098-4103
Number of pages6
JournalJournal of Immunology
Volume167
Issue number7
Publication statusPublished - Oct 1 2001
Externally publishedYes

Fingerprint

Immediate-Early Genes
Fas Ligand Protein
Cytomegalovirus
Retina
Up-Regulation
Apoptosis
Retinitis
Infection
Acquired Immunodeficiency Syndrome
Jurkat Cells
Viral Genes
Retinal Pigment Epithelium
Blindness
In Situ Hybridization
Cultured Cells
Cell Death
Immunohistochemistry

ASJC Scopus subject areas

  • Immunology

Cite this

Up-regulation of Fas ligand expression by human cytomegalovirus immediate-early gene product 2 : A novel mechanism in cytomegalovirus-induced apoptosis in human retina. / Chiou, S. H.; Liu, J. H.; Hsu, Wen-Ming; Chen, S. S L; Chang, S. Y.; Juan, L. J.; Lin, J. C.; Yang, Y. T.; Wong, W. W.; Liu, C. Y.; Lin, Y. S.; Liu, W. T.; Wu, C. W.

In: Journal of Immunology, Vol. 167, No. 7, 01.10.2001, p. 4098-4103.

Research output: Contribution to journalArticle

Chiou, SH, Liu, JH, Hsu, W-M, Chen, SSL, Chang, SY, Juan, LJ, Lin, JC, Yang, YT, Wong, WW, Liu, CY, Lin, YS, Liu, WT & Wu, CW 2001, 'Up-regulation of Fas ligand expression by human cytomegalovirus immediate-early gene product 2: A novel mechanism in cytomegalovirus-induced apoptosis in human retina', Journal of Immunology, vol. 167, no. 7, pp. 4098-4103.
Chiou, S. H. ; Liu, J. H. ; Hsu, Wen-Ming ; Chen, S. S L ; Chang, S. Y. ; Juan, L. J. ; Lin, J. C. ; Yang, Y. T. ; Wong, W. W. ; Liu, C. Y. ; Lin, Y. S. ; Liu, W. T. ; Wu, C. W. / Up-regulation of Fas ligand expression by human cytomegalovirus immediate-early gene product 2 : A novel mechanism in cytomegalovirus-induced apoptosis in human retina. In: Journal of Immunology. 2001 ; Vol. 167, No. 7. pp. 4098-4103.
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abstract = "Human CMV (HCMV) is an important pathogen that causes widespread diseases in immunocompromised individuals. Among the opportunistic HCMV infections, HCMV retinitis is most common in transplant recipients and AIDS patients. It often leads to blindness if left untreated. The question as to how HCMV infection causes retinal pathogenesis remains unresolved. Here, we report that viral immediate-early gene product 2 (IE2), but not IE1, up-regulates the Fas ligand (FasL) expression in HCMVinfected human retinal pigment epithelium cells. Increased secretion of FasL from virally infected cells into cultured medium was observed upon HCMV infection. The capability of such cell-free medium to induce apoptosis of Fas (CD95)-expressing Jurkat cells further implies that Fas-FasL interaction might mediate cell death in the lesion of HCMV retinitis. To support this idea, we observed augmented soluble FasL levels in vitreous from AIDS patients with HCMV retinitis as compared with that from AIDS patients without HCMV infection. In addition, by in situ hybridization and immunohistochemistry, we detected enhanced signals of FasL, the existence of viral IE Ags and apoptotic cells at the same sites in the lesion of HCMV-infected retina. These results strongly suggest that IE2 induction of FasL expression in human retina might be an important event that takes place in the early stage of infection and finally leads to visual loss in individuals affiliated with HCMV retinitis.",
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