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Updated: Mar 17, 2026
Use of In vivo Imaging to Monitor the Progression of Experimental Mouse Cytomegalovirus Infection in Neonates
Published on: July 6, 2013
Cytomegalovirus Infection of the Rat Developing Brain In Utero Prominently Targets Immune Cells and Promotes Early
Robin Cloarec1,2,3, Sylvian Bauer1,2,3, Hervé Luche4,5,6
1INSERM U901, Marseille, France.
Background:
Congenital cytomegalovirus infections are a leading cause of neurodevelopmental disorders in human and represent a major health care and socio-economical burden. In contrast with this medical importance, the pathophysiological events remain poorly known. Murine models of brain cytomegalovirus infection, mostly neonatal, have brought recent insights into the possible pathogenesis, with convergent evidence for the alteration and possible involvement of brain immune cells.
Objectives And Methods:
In order to confirm and expand those findings, particularly concerning the early developmental stages following infection of the fetal brain, we have created a model of in utero cytomegalovirus infection in the developing rat brain. Rat cytomegalovirus was injected intraventricularly at embryonic day 15 (E15) and the brains analyzed at various stages until the first postnatal day, using a combination of gene expression analysis, immunohistochemistry and multicolor flow cytometry experiments.
Results:
Rat cytomegalovirus infection was increasingly seen in various brain areas including the choroid plexi and the ventricular and subventricular areas and was prominently detected in CD45low/int, CD11b+ microglial cells, in CD45high, CD11b+ cells of the myeloid lineage including macrophages, and in CD45+, CD11b- lymphocytes and non-B non-T cells. In parallel, rat cytomegalovirus infection of the developing rat brain rapidly triggered a cascade of pathophysiological events comprising: chemokines upregulation, including CCL2-4, 7 and 12; infiltration by peripheral cells including B-cells and monocytes at E17 and P1, and T-cells at P1; and microglia activation at E17 and P1.
Conclusion:
In line with previous findings in neonatal murine models and in human specimen, our study further suggests that neuroimmune alterations might play critical roles in the early stages following cytomegalovirus infection of the brain in utero. Further studies are now needed to determine which role, whether favorable or detrimental, those putative double-edge swords events actually play.
Insights
Congenital cytomegalovirus (CMV) infection in the developing brain triggers neuroinflammation and immune cell infiltration. This study reveals early pathophysiological events in a rat model, highlighting the role of neuroimmune alterations in fetal CMV brain infections.
Area of Science:
- Neuroscience
- Immunology
- Developmental Biology
Background:
- Congenital cytomegalovirus (CMV) infection is a primary cause of neurodevelopmental disorders.
- Pathophysiology of CMV brain infections, especially in early development, is poorly understood.
- Murine models suggest brain immune cell involvement in CMV pathogenesis.
Purpose of the Study:
- To investigate early pathophysiological events following in utero cytomegalovirus (CMV) infection in the developing rat brain.
- To expand knowledge on CMV pathogenesis during critical fetal developmental stages.
- To characterize the immune response within the fetal brain after CMV exposure.
Main Methods:
- Intraventricular injection of rat CMV into embryonic day 15 (E15) rat brains.
- Analysis of brain tissue at various stages until postnatal day 1 (P1).
- Utilized gene expression analysis, immunohistochemistry, and multicolor flow cytometry.
Main Results:
- Rat CMV infection detected in various brain regions, notably in microglial cells, myeloid lineage cells, lymphocytes, and non-B/non-T cells.
- Rapid induction of chemokines (CCL2-4, 7, 12) observed.
- Infiltration of peripheral immune cells (B-cells, monocytes, T-cells) and microglia activation occurred early post-infection.
Conclusions:
- Neuroimmune alterations are critical in early stages of in utero CMV brain infection.
- Findings align with previous studies in murine models and human samples.
- Further research is needed to elucidate the precise role of these neuroimmune events in congenital CMV disease.
