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Published on: March 10, 2023
Retinal and Choroidal Pathologies in Aged BALB/c Mice Following Systemic Neonatal Murine Cytomegalovirus Infection
Jinxian Xu1, Xinglou Liu1, Xinyan Zhang1
1Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia; James and Jean Vision Discovery Institute, Medical College of Georgia, Augusta University, Augusta, Georgia.
Abstract:
Although pathologies associated with acute virus infections have been extensively studied, the effects of long-term latent virus infections are less well understood. Human cytomegalovirus, which infects 50% to 80% of humans, is usually acquired during early life and persists in a latent state for the lifetime. The purpose of this study was to determine whether systemic murine cytomegalovirus (MCMV) infection acquired early in life disseminates to and becomes latent in the eye and if ocular MCMV can trigger in situ inflammation and occurrence of ocular pathology. This study found that neonatal infection of BALB/c mice with MCMV resulted in dissemination of virus to the eye, where it localized principally to choroidal endothelia and pericytes and less frequently to the retinal pigment epithelium (RPE) cells. MCMV underwent ocular latency, which was associated with expression of multiple virus genes and from which MCMV could be reactivated by immunosuppression. Latent ocular infection was associated with significant up-regulation of several inflammatory/angiogenic factors. Retinal and choroidal pathologies developed in a progressive manner, with deposits appearing at both basal and apical aspects of the RPE, RPE/choroidal atrophy, photoreceptor degeneration, and neovascularization. The pathologies induced by long-term ocular MCMV latency share features of previously described human ocular diseases, such as age-related macular degeneration.
Insights
Neonatal murine cytomegalovirus (MCMV) infection establishes lifelong latency in the eye. This latent ocular MCMV triggers inflammation and progressive retinal pathologies, mimicking human eye diseases.
Area of Science:
- Virology
- Ophthalmology
- Immunology
Background:
- Long-term effects of latent virus infections are understudied.
- Human cytomegalovirus (HCMV) is a widespread latent virus.
- Ocular pathologies can arise from latent viral infections.
Purpose of the Study:
- To investigate if systemic murine cytomegalovirus (MCMV) infection disseminates to the eye and establishes latency.
- To determine if latent ocular MCMV triggers inflammation and pathology.
- To compare induced pathologies with human ocular diseases.
Main Methods:
- Neonatal BALB/c mice were infected with MCMV.
- Ocular tissues were analyzed for viral dissemination and latency.
- Gene expression of inflammatory and angiogenic factors was assessed.
- Ocular pathology development was monitored over time.
Main Results:
- MCMV disseminated to the eye, localizing to choroidal endothelia and pericytes.
- Ocular MCMV established latency, reactivated by immunosuppression, and expressed viral genes.
- Latent infection led to up-regulation of inflammatory/angiogenic factors.
- Progressive retinal and choroidal pathologies, including RPE changes, atrophy, degeneration, and neovascularization, were observed.
Conclusions:
- Early-life systemic MCMV infection leads to latent ocular infection.
- Latent ocular MCMV induces chronic inflammation and progressive retinal pathologies.
- These MCMV-induced pathologies resemble human age-related macular degeneration and other ocular diseases.
