Details

Autor(en) / Beteiligte

• Sun, Guoqiang
• Chiuppesi, Flavia
• Chen, Xianwei
• Wang, Cheng
• Tian, E
• Nguyen, Jenny
• Kha, Mindy
• Trinh, Daniel
• Zhang, Hannah
• Marchetto, Maria C.
• Song, Hongjun
• Ming, Guo-Li
• Gage, Fred H.
• Diamond, Don J.
• Wussow, Felix
• Shi, Yanhong

Titel

Modeling Human Cytomegalovirus-Induced Microcephaly in Human iPSC-Derived Brain Organoids

Ist Teil von

• Cell reports. Medicine, 2020-04, Vol.1 (1), p.100002-100002, Article 100002

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2020

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Although congenital infection by human cytomegalovirus (HCMV) is well recognized as a leading cause of neurodevelopmental defects, HCMV neuropathogenesis remains poorly understood. A major challenge for investigating HCMV-induced abnormal brain development is the strict CMV species specificity, which prevents the use of animal models to directly study brain defects caused by HCMV. We show that infection of human-induced pluripotent-stem-cell-derived brain organoids by a “clinical-like” HCMV strain results in reduced brain organoid growth, impaired formation of cortical layers, and abnormal calcium signaling and neural network activity. Moreover, we show that the impeded brain organoid development caused by HCMV can be prevented by neutralizing antibodies (NAbs) that recognize the HCMV pentamer complex. These results demonstrate in a three-dimensional cellular biosystem that HCMV can impair the development and function of the human brain and provide insights into the potential capacity of NAbs to mitigate brain defects resulted from HCMV infection. [Display omitted] Human iPSC-derived brain organoids to model HCMV-induced brain malformation“Clinical-like” HCMV strain impairs human brain organoid growth and structureHCMV-infected brain organoids exhibit abnormal calcium signaling and neural networkHCMV-induced brain organoid abnormality can be prevented by neutralizing antibodies Sun et al. used human-iPSC-derived brain organoids to model the effects of HCMV infection on human brain development. They found that a “clinical-like” HCMV strain impairs brain organoid growth, structure, and neural network activity. Moreover, the abnormal brain organoid development caused by HCMV can be prevented by neutralizing antibodies.