Downregulation of neurodevelopmental gene expression in iPSC-derived cerebral organoids upon infection by human cytomegalovirus

iScience

Scott S. Terhune¹  Kirthi Pulakanti²  Benjamin S. O’Brien³  Sridhar Rao³  Rebekah L. Mokry⁴  Allison D. Ebert⁴  Megan L. Schumacher⁴ 

[1] Blood Research Institute, Versiti, Milwaukee, WI 53226, USA;Blood Research Institute, Versiti, Milwaukee, WI 53226, USA;Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA;Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI 53226, USA;

关键词: Biotechnology;    Developmental neuroscience;    Transcriptomics;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: Human cytomegalovirus (HCMV) is a betaherpesvirus that can cause severe birth defects including vision and hearing loss, microcephaly, and seizures. Currently, no approved treatment options exist for in utero infections. Here, we aimed to determine the impact of HCMV infection on the transcriptome of developing neurons in an organoid model system. Cell populations isolated from organoids based on a marker for infection and transcriptomes were defined. We uncovered downregulation in key cortical, neurodevelopmental, and functional gene pathways which occurred regardless of the degree of infection. To test the contributions of specific HCMV immediate early proteins known to disrupt neural differentiation, we infected NPCs using a recombinant virus harboring a destabilization domain. Despite suppressing their expression, HCMV-mediated transcriptional downregulation still occurred. Together, our studies have revealed that HCMV infection causes a profound downregulation of neurodevelopmental genes and suggest a role for other viral factors in this process.

【 授权许可】

Unknown