title: Human cytomegalovirus retinitis: pathogenicity, immune evasion and persistence.
abstract: Human cytomegalovirus (HCMV) retinitis frequently occurs in severely naturally and iatrogenically immunocompromised patients. It has been shown that the immune-privileged retinal pigment epithelium (RPE) is a major site of persistent HCMV. Recently, evidence has accumulated to show that HCMV immediate early (IE) gene expression in RPE cells deviates ocular antiviral inflammation via FasL. Moreover, unlike in other cell types, the HCMV major IE1/2 enhancer promoter (MIEP) resists activation by proinflammatory stimuli mediated by the transcription factor NF-kappaB. However, tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) found at elevated levels in transplant recipients and AIDS patients with retinitis sensitize RPE cells and other retinal cells to FasL-mediated apoptosis, thus contributing to retina destruction and necrosis rather than inflammation. These specific features of RPE cells in conjunction with deregulated immune responses of immunocompromised patients seem to contribute to virus persistence and pathogenesis within the immune-privileged ocular retina.
authors.affiliation: Zentrum der Hygiene, Institut für Medizinische Virologie, Klinikum der Johann Wolfgang Goethe-Universität, Paul-Ehrlich-Strasse 40, D-60596 Frankfurt am Main, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Scholz
authors.forename: Hans Wilhelm
authors.initials: HW
authors.lastname: Doerr
authors.forename: Jindrich
authors.initials: J
authors.lastname: Cinatl
mesh_terms: D003587:Cytomegalovirus / Q000276:immunology* / Q000502:physiology; D017726:Cytomegalovirus Retinitis / Q000150:complications / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D016867:Immunocompromised Host; D010857:Pigment Epithelium of Eye / Q000201:enzymology / Q000378:metabolism / Q000821:virology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014779:Virus Replication
chemical_list: D014409:Tumor Necrosis Factor-alpha