Occurrence of Cytomegalovirus Retinitis After Human Immunodeficiency Virus Immunosuppression

Hoover, Donald R.; Peng, Yun; Saah, Alfred J.; Semba, Richard D.; Detels, Roger; Rinaldo, Charles R.; Phair, John P.

doi:10.1001/archopht.1996.01100140035004

Cited by 185 publications

(76 citation statements)

References 20 publications

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“…Although the initial symptoms and signs of infection are minimal and often ignored, the destructive and invasive nature of HCMV retinitis can result in blindness if left untreated (3,4,21). However, up to date, the pathogenic pathway of the underlying mechanism has not been completely established.…”

Section: Discussionmentioning

confidence: 99%

“…If transmission of HCMV in retina is through cell-cell contacts, the focal infection would be the major pattern and nercotizing retina could be limited in a small area. However, the progression of HCMV retinitis is rapidly spreading into nearby tissues (21). It is likely that viral products or factors released from infected cells mediate the cell death observed in the lesions of HCMV retinitis.…”

Section: Discussionmentioning

confidence: 99%

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Up-Regulation of Fas Ligand Expression by Human Cytomegalovirus Immediate-Early Gene Product 2: A Novel Mechanism in Cytomegalovirus-Induced Apoptosis in Human Retina

Chiou¹,

Liu²,

Hsu³

et al. 2001

The Journal of Immunology

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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 HCMV-infected 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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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Up-Regulation of Fas Ligand Expression by Human Cytomegalovirus Immediate-Early Gene Product 2: A Novel Mechanism in Cytomegalovirus-Induced Apoptosis in Human Retina

Chiou¹,

Liu²,

Hsu³

et al. 2001

The Journal of Immunology

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“…Median time to progression was 47 to 104 days, mean survival after diagnosis was six to 10 months, and indefinite intravenous maintenance therapy was mandatory 12 . It leads to blindness in nearly all untreated cases, has a high rate of short-term relapse and is strongly associated with higher mortality 1,10,15,17,34,38 .…”

Section: Introductionmentioning

confidence: 99%

Withdrawal of maintenance therapy for cytomegalovirus retinitis in AIDS patients exhibiting immunological response to HAART

Waib

Bonon

Salles

et al. 2007

Rev. Inst. Med. trop. S. Paulo

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SUMMARYBackground: Before the introduction of highly active antiretroviral therapy (HAART), CMV retinitis was a common complication in patients with advanced HIV disease and the therapy was well established; it consisted of an induction phase to control the infection with ganciclovir, followed by a lifelong maintenance phase to avoid or delay relapses. Methods: To determine the safety of CMV maintenance therapy withdrawal in patients with immune recovery after HAART, 35 patients with treated CMV retinitis, on maintenance therapy, with CD4+ cell count greater than 100 cells/mm 3 for at least three months, but almost all patients presented these values for more than six months and viral load < 30000 copies/mL, were prospectively evaluated for the recurrence of CMV disease. Maintenance therapy was withdrawal at inclusion, and patients were monitored for at least 48 weeks by clinical and ophthalmologic evaluations, and by determination of CMV viremia markers (antigenemia-pp65), CD4+/CD8+ counts and plasma HIV RNA levels. Lymphoproliferative assays were performed on 26/35 patients. Results: From 35 patients included, only one had confirmed reactivation of CMV retinitis, at day 120 of follow-up. No patient returned positive antigenemia tests. No correlation between lymphoproliferative assays and CD4+ counts was observed. Conclusion: CMV retinitis maintenance therapy discontinuation is safe for those patients with quantitative immune recovery after HAART.

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“…The anatomical site of HCMV disease varies according to the nature of the patient group, implying that each immunocompromised host may make unique contributions to disease pathogenesis. Thus, bone marrow transplant recipients frequently experience HCMV pneumonitis and gastrointestinal tract disease (Nichols & Boeckh 2000); solid organ recipients experience hepatitis, gastrointestinal tract disease and prolonged fever (Ho 1994), while HIV-infected individuals with CD4 cell counts less than 50 cells ml K1 predominantly experience HCMV retinitis (Dunn & Jabs 1995;Hoover et al 1996).…”

Section: Introductionmentioning

confidence: 99%

Modelling cytomegalovirus replication patterns in the human host: factors important for pathogenesis

et al. 2006

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Human cytomegalovirus can cause a diverse range of diseases in different immunocompromised hosts. The pathogenic mechanisms underlying these diseases have not been fully elucidated, though the maximal viral load during infection is strongly correlated with the disease. However, concentrating on single viral load measures during infection ignores valuable information contained during the entire replication history up to the onset of disease. We use a statistical model that allows all viral load data sampled during infection to be analysed, and have applied it to four immunocompromised groups exhibiting five distinct cytomegalovirus-related diseases. The results show that for all diseases, peaks in viral load contribute less to disease progression than phases of low virus load with equal amount of viral turnover. The model accurately predicted the time of disease onset for fever, gastrointestinal disease and pneumonitis but not for hepatitis and retinitis, implying that other factors may be involved in the pathology of these diseases.

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Occurrence of Cytomegalovirus Retinitis After Human Immunodeficiency Virus Immunosuppression

Cited by 185 publications

References 20 publications

Up-Regulation of Fas Ligand Expression by Human Cytomegalovirus Immediate-Early Gene Product 2: A Novel Mechanism in Cytomegalovirus-Induced Apoptosis in Human Retina

Up-Regulation of Fas Ligand Expression by Human Cytomegalovirus Immediate-Early Gene Product 2: A Novel Mechanism in Cytomegalovirus-Induced Apoptosis in Human Retina

Withdrawal of maintenance therapy for cytomegalovirus retinitis in AIDS patients exhibiting immunological response to HAART

Modelling cytomegalovirus replication patterns in the human host: factors important for pathogenesis

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