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. 2017 Apr 24;32(3):188–198. doi: 10.1007/s12250-017-3956-0

Human cytomegalovirus infection dysregulates neural progenitor cell fate by disrupting Hes1 rhythm and down-regulating its expression

Xi-Juan Liu 1,2, Xuan Jiang 1,3, Sheng-Nan Huang 1, Jin-Yan Sun 1, Fei Zhao 1, Wen-Bo Zeng 1,✉, Min-Hua Luo 1,✉
PMCID: PMC6598910  PMID: 28451898

Abstract

Human cytomegalovirus (HCMV) infection is a leading cause of birth defects, primarily affecting the central nervous system and causing its maldevelopment. As the essential downstream effector of Notch signaling pathway, Hes1, and its dynamic expression, plays an essential role on maintaining neural progenitor /stem cells (NPCs) cell fate and fetal brain development. In the present study, we reported the first observation of Hes1 oscillatory expression in human NPCs, with an approximately 1.5 hour periodicity and a Hes1 protein half-life of about 17 (17.6 ± 0.2) minutes. HCMV infection disrupts the Hes1 rhythm and down-regulates its expression. Furthermore, we discovered that depleting Hes1 protein disturbed NPCs cell fate by suppressing NPCs proliferation and neurosphere formation, and driving NPCs abnormal differentiation. These results suggested a novel mechanism linking disruption of Hes1 rhythm and down-regulation of Hes1 expression to neurodevelopmental disorders caused by congenital HCMV infection.

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Keywords: human cytomegalovirus (HCMV), neural progenitor cells (NPCs), Hes1 rhythm, cell fate

Acknowledgments

This work was supported by the National Natural Science Foundation of China (31600145).

Contributor Information

Wen-Bo Zeng, Email: zengwb@wh.iov.cn.

Min-Hua Luo, Email: luomh@wh.iov.cn.

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