July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Murine cytomegalovirus (MCMV) disseminates to and remains latent in the choroid following systemic infection of neonatal BALB/c mice
Author Affiliations & Notes
  • Ming Zhang
    Department of Cellular Biology and Anatomy, Augusta University, Augusta, Georgia, United States
  • Jinxian Xu
    Department of Cellular Biology and Anatomy, Augusta University, Augusta, Georgia, United States
  • Xinglou Liu
    Department of Cellular Biology and Anatomy, Augusta University, Augusta, Georgia, United States
  • Brendan Marshall
    Department of Cellular Biology and Anatomy, Augusta University, Augusta, Georgia, United States
  • Zheng Dong
    Department of Cellular Biology and Anatomy, Augusta University, Augusta, Georgia, United States
  • Footnotes
    Commercial Relationships   Ming Zhang, None; Jinxian Xu, None; Xinglou Liu, None; Brendan Marshall, None; Zheng Dong, None
  • Footnotes
    Support  NIH grant EY026642
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 718. doi:
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      Ming Zhang, Jinxian Xu, Xinglou Liu, Brendan Marshall, Zheng Dong; Murine cytomegalovirus (MCMV) disseminates to and remains latent in the choroid following systemic infection of neonatal BALB/c mice
      . Invest. Ophthalmol. Vis. Sci. 2018;59(9):718.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Age-related macular degeneration (AMD) is the leading cause of blindness worldwide. Environmental and genetic risk-factors implicate chronic inflammation in the etiology of AMD. Chronic infection with human cytomegalovirus (HCMV) is shown to be a novel risk factor for the progression of AMD. The purpose of this study was to determine if systemic murine cytomegalovirus (MCMV) disseminates to and becomes latent in the choroid and if the latent MCMV in the choroid can be reactivated in vitro.

Methods : Newborn BALB/c mice were inoculated with 50 pfu of MCMV via the peritoneal route. At intervals post infection (p.i.), mice were sacrificed and eyes and extraocular tissues were collected for analysis by plaque assay to quantify replicating virus, by PCR for viral gene expression, and by immunohistochemical staining or by immunogold EM for MCMV early antigen (EA) expression. At day 90 p.i., some eyes from BALB/c mice were placed in culture plate inserts and co-cultivated with MEF cells to detect reactivated MCMV. Also at day 90 p.i., posterior eye cups from BALB/c mice were cultured at 37°C. Culture medium was collected bi-weekly and examined by plaque assay for replicating virus. Cultures were also harvested and stained for MCMV EA.

Results : Replicating virus was detected in the lungs, salivary glands as well as in the eyes (7/7) at day 14 p.i. No replicating virus was detected in brains. MCMV EA was observed in the nuclei of vascular endothelial cells and pericytes in the choriocapillaris. In addition, a few RPE cells also stained positive for MCMV EA. No replicating virus was detected in the eyes, salivary glands or lungs at day 90 p.i., although virus DNA was still detected in eyes (9/9) and extraocular tissues. After 2 weeks of co-cultivation with MEF, virus was recovered from 2 of 10 eyes. After 6 weeks in culture, reactivated virus was recovered from 7 of 10 eyes. Virus was also detected in the culture medium of eye cup cultures starting at day 7 of culture (1/8). After 3 weeks in culture, virus was detected in 7 of 8 samples. In addition, MCMV EA was detected in the choroid and RPE layers in eye cup cultures.

Conclusions : MCMV disseminates to and remains latent in the choroid following systemic infection of neonatal BALB/c mice. Choroid infection or reactivation of MCMV in the eye cup may be a trigger for in situ inflammation.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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