Cytomegalovirus establishes a latent reservoir and triggers long-lasting inflammation in the eye

Abstract

Recent outbreaks of Ebola and Zika have highlighted the possibility that viruses may cause enduring infections in tissues like the eye, including the neural retina, which have been considered immune privileged. Whether this is a peculiarity of exotic viruses remains unclear, since the impact of more common viral infections on neural compartments has not been examined, especially in immunocompetent hosts. Cytomegalovirus is a common, universally distributed pathogen, generally innocuous in healthy individuals. Whether in immunocompetent hosts cytomegalovirus can access the eye, and reside there indefinitely, was unknown. Using the well-established murine cytomegalovirus infection model, we show that systemic infection of immunocompetent hosts results in broad ocular infection, chronic inflammation and establishment of a latent viral pool in the eye. Infection leads to infiltration and accumulation of anti-viral CD8+ T cells in the eye, and to the development of tissue resident memory T cells that localize to the eye, including the retina. These findings identify the eye as an unexpected reservoir for cytomegalovirus, and suggest that common viruses may target this organ more frequently than appreciated. Notably, they also highlight that infection triggers sustained inflammatory responses in the eye, including the neural retina.

Ebola virus and persistent chronic infection: when does replication cease?

“…A myeloid cell niche has been proposed as a common mechanism for viral persistence in other infections such as Dengue, Chikungunya and Marburg virus (7). In the case of DNA viruses such as CMV, viral targeting of myeloid cells is a prominent mechanism for achieving latent infection (20).…”

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

“…However, there have been con icting reports regarding whether MCMV can undergo ocular latency following systemic infection, with several studies reporting that immunosuppression is required for intraocular viral replication after systemic MCMV infection 23,43,44 while others have reported that MCMV DNA could not be detected within eye tissues of immunocompetent adult C57BL/6 mice several months post systemic MCMV infection 20 . A study by Bale et al reported that latent ocular MCMV could be detected in 10% of mice infected with MCMV via the intraperitoneal route 45 while a recent study from Voigt et al 46 showed that MCMV spread to the eye following i.p. inoculation of adult BALB/c mice with 1x10 4 PFU, resulting in latent infection in both the iris (26%) and choroid (22%).…”

Validating Fluorescent Chrnb4.EGFP Mouse Models for the Study of Cone Photoreceptor Degeneration

“…Retinal wholemounts for CD45 and collagen IV staining followed a previously published protocol. 31 Image acquisition was done on a Nikon A1Si confocal microscope and images captured on an Andor 885 EMCCD camera with the NIS Elements imaging software.…”

“…Data from 6-month-old mouse retinas for average GFP + cell quantification were obtained after the papain dissociation protocol (minimum of n = 5 per mouse line). The trypsin and liberase protocols were taken from previously published studies, 31,33,34 while the papain protocol was adapted from Barber et al 35 as follows. Freshly dissected retinal sample were incubated in a 1:20 solution of papain/DNase (Worthington Biochemicals, LK003176/LK003170) at 37°C for 45min and gently triturated.…”