Related Experiment Video
Updated: Jun 7, 2025
Use of In vivo Imaging to Monitor the Progression of Experimental Mouse Cytomegalovirus Infection in Neonates
Published on: July 6, 2013
Immune responses drive chorioretinitis and retinal pathology after neonatal CMV infection
Jessica L McCord1, John Y S Han2, Ross E Staudt1
1Department of Microbiology and Immunology, Jefferson Center for Vaccines and Pandemic Preparedness, Sidney Kimmel Medical College, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
Abstract:
Human cytomegalovirus (CMV) causes a common congenital infection leading to long-term neurological impairments including brain, cochlear, and ocular pathology. Infection of newborn mice with murine (M)CMV is an established model of neuropathology caused by congenital CMV infection, with recent work suggesting that brain pathology may be driven by immune responses. In the eye, however, CMV retinitis is thought to result from virus-driven necrosis in the absence of T cell responses. We found that MCMV infection of newborn mice recapitulates human eye disease after congenital CMV infection, including focal chorioretinitis, inflamed vasculature, and disrupted blood-retinal barriers. Moreover, infection drove extensive T cell infiltration of the retina and marked gliosis. Blocking immune responses generally, or via targeting the chemokine receptor CXCR3, did not exacerbate retinal disease but instead prevented pathology despite retinal MCMV infection. Thus, our data establish this model for studies of congenital retinal disease and show that the immune system drives pathology in the neonatal eye after MCMV infection.
Insights
Congenital human cytomegalovirus (CMV) infection causes neurological issues. Murine CMV infection in newborn mice shows the immune system drives eye pathology, not just the virus.
Area of Science:
- Virology
- Immunology
- Ophthalmology
Background:
- Congenital human cytomegalovirus (CMV) infection is a leading cause of non-genetic sensorineural hearing loss and neurodevelopmental disability.
- Murine cytomegalovirus (MCMV) infection in newborn mice serves as a model for congenital CMV neuropathology.
- Current understanding suggests CMV retinitis results from virus-driven necrosis, independent of T cell responses.
Purpose of the Study:
- To establish a murine model for congenital CMV ocular disease.
- To investigate the role of immune responses in MCMV-induced retinal pathology.
- To determine if T cell responses contribute to ocular disease in congenital MCMV infection.
Main Methods:
- Infection of newborn mice with MCMV.
- Histopathological analysis of retinal tissues.
- Assessment of immune cell infiltration and gliosis.
- Pharmacological blockade of immune responses, including CXCR3 inhibition.
Main Results:
- MCMV infection in mice recapitulated key features of human congenital CMV eye disease, including chorioretinitis, vascular inflammation, and blood-retinal barrier disruption.
- Retinal infection led to significant T cell infiltration and gliosis.
- Blocking immune responses, particularly targeting CXCR3, ameliorated retinal pathology despite ongoing MCMV infection.
Conclusions:
- The MCMV-infected newborn mouse is a suitable model for studying congenital retinal disease.
- Immune responses, rather than direct viral necrosis, are the primary drivers of pathology in the neonatal eye during MCMV infection.
- Targeting specific immune pathways may offer therapeutic strategies for congenital CMV-induced ocular disease.
More Related Videos
05:51Intracerebroventricular and Intravascular Injection of Viral Particles and Fluorescent Microbeads into the Neonatal Brain
Published on: July 24, 2016
08:50A Murine Model of Fetal Exposure to Maternal Inflammation to Study the Effects of Acute Chorioamnionitis on Newborn Intestinal Development
Published on: June 24, 2020
