Cytomegalovirus-induced brain malformations in fetuses

Area of Science:

• Neuropathology
• Developmental Neuroscience
• Infectious Diseases

Background:

• Congenital cytomegalovirus (CMV) infection is a leading cause of non-genetic sensorineural hearing loss and neurodevelopmental disability.
• The precise mechanisms underlying CMV-induced neuropathology in fetal brains are not fully understood.

Purpose of the Study:

• To investigate the neuropathologic substrates, immune response, and cellular targets of CMV in human fetal brains.
• To elucidate the factors contributing to the spectrum of brain abnormalities in congenital CMV infection.

Main Methods:

• Analysis of 16 human fetal brains (23-28.5 weeks gestation) infected with CMV.
• Neuropathologic examination, including assessment of microcephaly, cortical and hippocampal lesions, and olfactory bulb infection.
• Immunolabeling to quantify CMV-infected cells and characterize immune responses and cellular tropism.

Main Results:

• CMV infection was associated with microcephaly, cortical lesions, hippocampal abnormalities, and olfactory bulb involvement.
• The density of CMV-infected cells correlated with the severity of microcephaly and brain abnormalities.
• CMV infected all cell types, with a higher tropism for stem cells/radial glial cells, and immune responses were present but not universally effective.

Conclusions:

• Neuropathologic outcomes in fetal brains are influenced by the density of CMV-infected cells and viral tropism for stem/progenitor cells.
• CMV-induced brain abnormalities result from both tissue destruction and the vulnerability of developing stem cells.
• Infection of the hippocampus and olfactory bulb may lead to long-term neurocognitive and sensorineural deficits, even with late-gestation infections.