A congenital CMV infection model for follow-up studies of neurodevelopmental disorders, neuroimaging abnormalities, and treatment

Yue Peng Zhou, Meng Jie Mei, Xian Zhang Wang, Sheng Nan Huang, Lin Chen, Ming Zhang, Xin Yan Li, Hai Bin Qin, Xiao Dong, Shuang Cheng, Le Wen, Xue Fang An, Ao Di He, Bing Zhang, Wen Bo Zeng, Xiao Jun Li, Youming Lu, Hong Chuang Li, Haidong Li, Wei Guo ZouAlec J. Redwood, Simon Rayner, Han Cheng, Michael A. McVoy, Qiyi Tang, William J. Britt, Xin Zhou, Xuan Jiang, Min Hua Luo, Bo Yang

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Congenital cytomegalovirus (cCMV) infection is the leading infectious cause of neurodevelopmental disorders. However, the neuropathogenesis remains largely elusive due to a lack of informative animal models. In this study, we developed a congenital murine CMV (cMCMV) infection mouse model with high survival rate and long survival period that allowed long-term follow-up study of neurodevelopmental disorders. This model involves in utero intracranial injection and mimics many reported clinical manifestations of cCMV infection in infants, including growth restriction, hearing loss, and impaired cognitive and learning-memory abilities. We observed that abnormalities in MRI/CT neuroimaging were consistent with brain hemorrhage and loss of brain parenchyma, which was confirmed by pathological analysis. Neuropathological findings included ventriculomegaly and cortical atrophy associated with impaired proliferation and migration of neural progenitor cells in the developing brain at both embryonic and postnatal stages. Robust inflammatory responses during infection were shown by elevated inflammatory cytokine levels, leukocyte infiltration, and activation of microglia and astrocytes in the brain. Pathological analyses and CT neuroimaging revealed brain calcifications induced by cMCMV infection and cell death via pyroptosis. Furthermore, antiviral treatment with ganciclovir significantly improved neurological functions and mitigated brain damage as shown by CT neuroimaging. These results demonstrate that this model is suitable for investigation of mechanisms of infection-induced brain damage and long-term studies of neurodevelopmental disorders, including the development of interventions to limit CNS damage associated with cCMV infection.

Original languageEnglish
Article numbere152551
JournalJCI Insight
Volume7
Issue number1
DOIs
Publication statusPublished - 11 Jan 2022

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