Downregulation of neurodevelopmental gene expression in iPSC-derived cerebral organoids upon infection by human cytomegalovirus. iScience 2022 Apr 15;25(4):104098
Date
04/09/2022Pubmed ID
35391828Pubmed Central ID
PMC8980761DOI
10.1016/j.isci.2022.104098Scopus ID
2-s2.0-85127531399 (requires institutional sign-in at Scopus site) 11 CitationsAbstract
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.
Author List
O'Brien BS, Mokry RL, Schumacher ML, Pulakanti K, Rao S, Terhune SS, Ebert ADAuthors
Allison D. Ebert PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinSridhar Rao MD, PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin
Scott Terhune PhD Professor in the Microbiology and Immunology department at Medical College of Wisconsin
