Characterization of a 52K protein of murine cytomegalovirus and its immunological cross-reactivity with the DNA-binding protein ICP36 of human cytomegalovirus

Pande, Hema; Campo, Karlene; Shanley, John D.; Creeger, E S; Artishevsky, Alexander; Gallez-Hawkins, Ghislaine; Zaia, John A.

doi:10.1099/0022-1317-72-6-1421

Cited by 16 publications

(7 citation statements)

References 15 publications

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“…Anti-MCMV early antigen (EA) 27 was used to identify MCMV-infected cells. The preparation and use of FITC-labeled anti-MCMV EA has been described elsewhere.…”

Section: Methodsmentioning

confidence: 99%

Depletion of the Receptor-Interacting Protein Kinase 3 (RIP3) Decreases Photoreceptor Cell Death During the Early Stages of Ocular Murine Cytomegalovirus Infection

Mao

Liu

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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PurposeThe purpose of this study was to determine if the receptor-interacting protein kinase 3 (RIP3) plays a significant role in innate immune responses and death of bystander retinal neurons during murine cytomegalovirus (MCMV) retinal infection, by comparing the innate immune response and cell death in RIP3-depleted mice (Rip3−/−) and Rip3+/+ control mice.MethodsRip3−/− and Rip3+/+ mice were immunosuppressed (IS) and inoculated with MCMV via the supraciliary route. Virus-injected and mock-injected control eyes were removed at days 4, 7, and 10 post infection (p.i.) and markers of innate immunity and cell death were analyzed.ResultsCompared to Rip3+/+ mice, significantly more MCMV was recovered and more MCMV-infected RPE cells were observed in injected eyes of Rip3−/− mice at days 4 and 7 p.i. In contrast, fewer TUNEL-stained photoreceptors were observed in Rip3−/− eyes than in Rip3+/+ eyes at these times. Electron microscopy showed that significantly more apoptotic photoreceptor cells were present in Rip3+/+ mice than in Rip3−/− mice. Immunohistochemistry showed that the majority of TUNEL-stained photoreceptors died via mitochondrial flavoprotein apoptosis-inducing factor (AIF)-mediated, caspase 3–independent apoptosis. The majority of RIP3-expressing cells in infected eyes were RPE cells, microglia/macrophages, and glia, whereas retinal neurons contained much lower amounts of RIP3. Western blots showed significantly higher levels of activated nuclear factor–κB and caspase 1 were present in Rip3+/+ eyes compared to Rip3−/− eyes.ConclusionsOur results suggest that RIP3 enhances innate immune responses against ocular MCMV infection via activation of the inflammasome and nuclear factor–κB, which also leads to inflammation and death of bystander cells by multiple pathways including apoptosis and necroptosis.

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“…Anti-MCMV early antigen (EA) 27 was used to identify MCMV-infected cells. The preparation and use of FITC-labeled anti-MCMV EA has been described elsewhere.…”

Section: Methodsmentioning

confidence: 99%

Depletion of the Receptor-Interacting Protein Kinase 3 (RIP3) Decreases Photoreceptor Cell Death During the Early Stages of Ocular Murine Cytomegalovirus Infection

Mao

Liu

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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“…The section was stained first with TUNEL (In Situ Cell Death Detection Kit, Fluorescein, Roche Diagnostics, Indianapolis, IN) according to the manufacturer's instructions. After washing and blocking, biotinylated anti-MCMV early antigen (EA) (Sulfo-NHS-LC-Biotin; Pierce, Rockford, IL) [1,34] was incubated in the section overnight at 4°C. Texas Red-labeled avidin (Vector Laboratories, Burlingame, CA) was then used to bind to Biotin for 1 hour at room temperature.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Autophagy protects against retinal cell death in mouse model of cytomegalovirus retinitis

Atherton

Wang

et al. 2019

Preprint

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Background: Extensive death of uninfected bystander neuronal cells is an important component of the pathogenesis of cytomegalovirus retinitis (CMV). Our previous results have shown that there is a functional relationship between autophagy and apoptosis during MCMV infection of retinal pigment epithelium (RPE). The purpose of this study was to determine whether autophagy plays a significant role in the death of retinal cells during MCMV retinitis. Methods: The retinas of adult BALB/c mice were infected with MCMV via supraciliary injection. Rapamycin was injected to MCMV-infected BALB/c mice intraperitoneally. Immunohistochemistry and western blot were performed to observe the spread pattern of virus in retinas and the levels of targeted proteins. Plaque assay was performed to determine the virus titer in different groups. Nestin-cre; Atg5flox/flox mice were genotyped and infected with MCMV. Immunohistochemistry was performed to observe the type of virus-infected cells and apoptosis in retinas during MCMV retinitis. Results: In MCMV mouse model, MCMV infection in our nuclear layer (ONL) and inner nuclear layer (INL) in the retinas caused cleaved caspase 3 positive apoptosis, which is not co-localized with early antigen (EA) positive virus infected cells in rapamycin treated group. Rapamycin treatment increased the levels of LC3B-II by inhibiting mTOR and decreased the levels of cleaved caspase-3 during MCMV retinitis. However, virus propagation was not affected by rapamycin. In Nestin-cre; Atg5flox/flox mice, RPE and glial cells were the main targets of viral infection, and number of EA positive retinal cells and TUNEL positive retinal cells was significantly increased compared to Nestin-cre; Atg5flox/+ mice though there was no difference of virus propagation between Nestin-cre; Atg5flox/flox mice and Nestin-cre; Atg5flox/+ mice. Conclusions: Autophagy protects retinal cells from MCMV infection induced apoptosis through mTOR-mediated signaling pathway.

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“…Antibodies. Anti-MCMV early antigen (EA) 65 was labeled with FITC (Sigma-Aldrich, St. Louis, MO) as previously described 66 . Anti-RPE65 was kindly provided by Dr. Michael Redmond (National Eye Institute, National Institutes of Health, Bethesda, MD).…”

Section: Methodsmentioning

confidence: 99%

Photoreceptor degeneration and choroidal neovascularization in aged BALB/c mice following systemic neonatal murine cytomegalovirus infection

Liu

Zhang

et al. 2020

Preprint

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Age-related macular degeneration (AMD) represents a leading cause of irreversible visual dysfunction in older individuals but its genesis is poorly understood. Human cytomegalovirus (HCMV), which infects 50 to 80% of humans, is usually acquired during early life and persists in a latent state for the life of the individual. Here we show that systemic neonatal murine cytomegalovirus (MCMV) infection of BALB/c mice resulted in dissemination of virus to the eye where it localized to choroidal endothelial cells and RPE cells. MCMV underwent ocular latency in all neonatally infected mice and latent/persistent ocular infection was associated with expression of MCMV immediate early genes, significant upregulation of several inflammatory/angiogenic factors. AMD–like pathology, including basal lamina deposits (BLamD), subretinal drusenoid deposits (SDD), severe photoreceptor degeneration, choroidal neovascularization (CNV) develop in eyes of latently-infected aged mice. Our study suggests a possible viral etiology for AMD as a result of latent/persistent ocular CMV infection.

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Characterization of a 52K protein of murine cytomegalovirus and its immunological cross-reactivity with the DNA-binding protein ICP36 of human cytomegalovirus

Cited by 16 publications

References 15 publications

Depletion of the Receptor-Interacting Protein Kinase 3 (RIP3) Decreases Photoreceptor Cell Death During the Early Stages of Ocular Murine Cytomegalovirus Infection

Depletion of the Receptor-Interacting Protein Kinase 3 (RIP3) Decreases Photoreceptor Cell Death During the Early Stages of Ocular Murine Cytomegalovirus Infection

Autophagy protects against retinal cell death in mouse model of cytomegalovirus retinitis

Photoreceptor degeneration and choroidal neovascularization in aged BALB/c mice following systemic neonatal murine cytomegalovirus infection

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