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Susceptibility of brain cells to murine cytomegalovirus infection in the developing mouse brain
Y Tsutsui1, A Kashiwai, N Kawamura
1Department of Pathology, Institute for Developmental Research, Aichi Prefectural Colony, Japan.
Abstract:
Mouse embryos were infected with murine cytomegalovirus (MCMV) by injecting the virus into the cerebral ventricles in the late stage of gestation; the brains of the offspring were than analyzed using the histological and immunohistochemical methods. Brains of the offspring, which were injected with relatively high titers of MCMV [1 X 10(4) plaque-forming units (pfu)] on day 13 of gestation exo utero or on day 15 of gestation in utero, showed massiv necrosis of the cerebral cortex with gliomesodermal proliferation around 9 to 10 days after birth. In these brains, viral antigen-positive cells were observed in zonal arrangement in the lesion-free cortex and in the hippocampus. Immunohistochemical double staining showed that some of the viral antigen-positive cells had also reacted with antibody to neuron-specific enolase at the same time, but had hardly reacted with antibodies to brain-type creatine kinase or glial fibrillary acidic protein. Brains of the offspring, which were injected with relatively low titers of virus (1 x 10(3) pfu) on day 15 of gestation, showed zonal arrangement of viral antigen-positive cells mainly in the cerebral cortex and in the hippocampus 7 days after birth, although the numbers of the positive cells were low. Fourteen days after birth, some of these offspring showed atrophy of the cerebral cortex and the hippocampus. These results suggest that some of the neuronal cells in the cerebral cortex and the hippocampus have special susceptibility to MCMV infection.
Insights
Murine cytomegalovirus (MCMV) infection in mouse embryos causes brain damage, including cerebral cortex necrosis and hippocampal atrophy. Neuronal cells in these brain regions show a particular susceptibility to MCMV infection.
Area of Science:
- Neuroscience
- Virology
- Developmental Biology
Background:
- Murine cytomegalovirus (MCMV) is a significant pathogen affecting the central nervous system.
- Congenital MCMV infection can lead to severe neurological sequelae.
- Understanding the specific cellular targets of MCMV in the developing brain is crucial.
Purpose of the Study:
- To investigate the neuropathological effects of MCMV infection in developing mouse brains.
- To identify the specific cell types susceptible to MCMV infection in the cerebral cortex and hippocampus.
- To correlate MCMV infection timing and viral titer with observed brain pathology.
Main Methods:
- Infection of mouse embryos with MCMV at different gestational stages and titers.
- Histological and immunohistochemical analysis of offspring brains.
- Double-staining techniques to identify viral antigen-positive cells and cell markers (neuron-specific enolase, brain-type creatine kinase, glial fibrillary acidic protein).
Main Results:
- High-titer MCMV infection led to cerebral cortex necrosis and gliomesodermal proliferation.
- Viral antigen-positive cells were found in the cortex and hippocampus, with some co-localizing with neuronal markers.
- Low-titer MCMV infection resulted in fewer viral-positive cells but caused cerebral cortex and hippocampal atrophy later in development.
Conclusions:
- Developing neuronal cells in the cerebral cortex and hippocampus exhibit a specific susceptibility to MCMV infection.
- The timing and dose of MCMV exposure influence the severity and type of neuropathology observed.
- These findings highlight the vulnerability of specific neuronal populations to viral insult during critical developmental periods.