Ocular reactivation of MCMV after immunosuppression of latently infected BALB/c mice

Ming Zhang, Hua Xin, Yanping Duan, Sally S. Atherton

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

PURPOSE. The purpose of this study was to identify the site(s) of MCMV latency and reactivation in the eye. METHODS. Three months after supraciliary inoculation of 5 × 10 2 PFU of MCMV, BALB/c mice underwent immunosuppression with methylprednisolone and antibodies specific for CD4 T cells, CD8 T cells, and NK cells or with methylprednisolone alone. Control mice were infected but did not receive the immunosuppressants. After 2 or 3 weeks of immunosuppression, the mice were killed. Replicating virus and viral antigen were detected in the injected eyes, peripheral blood leukocytes (PBLs), and extraocular tissues by plaque assay and by staining for early antigen (EA) and β-galactosidase (β-gal), respectively. RESULTS. In latently infected, nonimmunosuppressed control mice, replicating-virus-and viral-antigen-positive cells were not detected in the injected eyes or extraocular tissues. After immunosuppression with methylprednisolone and antibodies, EA and β-gal were detected, and replicating virus was recovered from the injected eye and from several extraocular sites, including liver, lungs, salivary glands, and kidneys. No virus was recovered from PBLs. β-Gal- or EA-positive cells were observed in the RPE of most mice, and a few virus-infected cells were also observed in the nuclear layers and ganglion cells. Microscopic changes, including retinal folding and detachment, photoreceptor atrophy, macrophage infiltration, and a few EA-positive cytomegalic cells, were observed in the injected eye of immunosuppressed mice. CONCLUSIONS. After immunosuppression, MCMV reactivates in the injected eye and extraocular tissues, and RPE cells are the initial site of MCMV ocular reactivation in the eye. The timing of virus recovery from all sites suggests that MCMV observed in the injected eye is from in situ reactivation of virus and not from spread of virus from extraocular sites via infected PBLs.

Original languageEnglish (US)
Pages (from-to)252-258
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume46
Issue number1
DOIs
StatePublished - Jan 1 2005

Fingerprint

Immunosuppression
Viruses
Methylprednisolone
Antigens
Leukocytes
Viral Antigens
Galactosidases
T-Lymphocytes
Antibodies
Retinal Detachment
Immunosuppressive Agents
Salivary Glands
Ganglia
Natural Killer Cells
Atrophy
Macrophages
Staining and Labeling
Kidney
Lung
Liver

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Ocular reactivation of MCMV after immunosuppression of latently infected BALB/c mice. / Zhang, Ming; Xin, Hua; Duan, Yanping; Atherton, Sally S.

In: Investigative Ophthalmology and Visual Science, Vol. 46, No. 1, 01.01.2005, p. 252-258.

Research output: Contribution to journalArticle

Zhang, Ming ; Xin, Hua ; Duan, Yanping ; Atherton, Sally S. / Ocular reactivation of MCMV after immunosuppression of latently infected BALB/c mice. In: Investigative Ophthalmology and Visual Science. 2005 ; Vol. 46, No. 1. pp. 252-258.
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abstract = "PURPOSE. The purpose of this study was to identify the site(s) of MCMV latency and reactivation in the eye. METHODS. Three months after supraciliary inoculation of 5 × 10 2 PFU of MCMV, BALB/c mice underwent immunosuppression with methylprednisolone and antibodies specific for CD4 T cells, CD8 T cells, and NK cells or with methylprednisolone alone. Control mice were infected but did not receive the immunosuppressants. After 2 or 3 weeks of immunosuppression, the mice were killed. Replicating virus and viral antigen were detected in the injected eyes, peripheral blood leukocytes (PBLs), and extraocular tissues by plaque assay and by staining for early antigen (EA) and β-galactosidase (β-gal), respectively. RESULTS. In latently infected, nonimmunosuppressed control mice, replicating-virus-and viral-antigen-positive cells were not detected in the injected eyes or extraocular tissues. After immunosuppression with methylprednisolone and antibodies, EA and β-gal were detected, and replicating virus was recovered from the injected eye and from several extraocular sites, including liver, lungs, salivary glands, and kidneys. No virus was recovered from PBLs. β-Gal- or EA-positive cells were observed in the RPE of most mice, and a few virus-infected cells were also observed in the nuclear layers and ganglion cells. Microscopic changes, including retinal folding and detachment, photoreceptor atrophy, macrophage infiltration, and a few EA-positive cytomegalic cells, were observed in the injected eye of immunosuppressed mice. CONCLUSIONS. After immunosuppression, MCMV reactivates in the injected eye and extraocular tissues, and RPE cells are the initial site of MCMV ocular reactivation in the eye. The timing of virus recovery from all sites suggests that MCMV observed in the injected eye is from in situ reactivation of virus and not from spread of virus from extraocular sites via infected PBLs.",
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N2 - PURPOSE. The purpose of this study was to identify the site(s) of MCMV latency and reactivation in the eye. METHODS. Three months after supraciliary inoculation of 5 × 10 2 PFU of MCMV, BALB/c mice underwent immunosuppression with methylprednisolone and antibodies specific for CD4 T cells, CD8 T cells, and NK cells or with methylprednisolone alone. Control mice were infected but did not receive the immunosuppressants. After 2 or 3 weeks of immunosuppression, the mice were killed. Replicating virus and viral antigen were detected in the injected eyes, peripheral blood leukocytes (PBLs), and extraocular tissues by plaque assay and by staining for early antigen (EA) and β-galactosidase (β-gal), respectively. RESULTS. In latently infected, nonimmunosuppressed control mice, replicating-virus-and viral-antigen-positive cells were not detected in the injected eyes or extraocular tissues. After immunosuppression with methylprednisolone and antibodies, EA and β-gal were detected, and replicating virus was recovered from the injected eye and from several extraocular sites, including liver, lungs, salivary glands, and kidneys. No virus was recovered from PBLs. β-Gal- or EA-positive cells were observed in the RPE of most mice, and a few virus-infected cells were also observed in the nuclear layers and ganglion cells. Microscopic changes, including retinal folding and detachment, photoreceptor atrophy, macrophage infiltration, and a few EA-positive cytomegalic cells, were observed in the injected eye of immunosuppressed mice. CONCLUSIONS. After immunosuppression, MCMV reactivates in the injected eye and extraocular tissues, and RPE cells are the initial site of MCMV ocular reactivation in the eye. The timing of virus recovery from all sites suggests that MCMV observed in the injected eye is from in situ reactivation of virus and not from spread of virus from extraocular sites via infected PBLs.

AB - PURPOSE. The purpose of this study was to identify the site(s) of MCMV latency and reactivation in the eye. METHODS. Three months after supraciliary inoculation of 5 × 10 2 PFU of MCMV, BALB/c mice underwent immunosuppression with methylprednisolone and antibodies specific for CD4 T cells, CD8 T cells, and NK cells or with methylprednisolone alone. Control mice were infected but did not receive the immunosuppressants. After 2 or 3 weeks of immunosuppression, the mice were killed. Replicating virus and viral antigen were detected in the injected eyes, peripheral blood leukocytes (PBLs), and extraocular tissues by plaque assay and by staining for early antigen (EA) and β-galactosidase (β-gal), respectively. RESULTS. In latently infected, nonimmunosuppressed control mice, replicating-virus-and viral-antigen-positive cells were not detected in the injected eyes or extraocular tissues. After immunosuppression with methylprednisolone and antibodies, EA and β-gal were detected, and replicating virus was recovered from the injected eye and from several extraocular sites, including liver, lungs, salivary glands, and kidneys. No virus was recovered from PBLs. β-Gal- or EA-positive cells were observed in the RPE of most mice, and a few virus-infected cells were also observed in the nuclear layers and ganglion cells. Microscopic changes, including retinal folding and detachment, photoreceptor atrophy, macrophage infiltration, and a few EA-positive cytomegalic cells, were observed in the injected eye of immunosuppressed mice. CONCLUSIONS. After immunosuppression, MCMV reactivates in the injected eye and extraocular tissues, and RPE cells are the initial site of MCMV ocular reactivation in the eye. The timing of virus recovery from all sites suggests that MCMV observed in the injected eye is from in situ reactivation of virus and not from spread of virus from extraocular sites via infected PBLs.

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