Human Cytomegalovirus Immediate Early 1 Protein Causes Loss of SOX2 from Neural Progenitor Cells by Trapping Unphosphorylated STAT3 in the Nucleus

作者：Cong-Cong Wu, Xuan Jiang, Xian-Zhang Wang, Xiaojian Liu, Xiaojun Li, Bo Yang, Han‐Qing Ye, Thomas Harwardt, Man Jiang, Huimin Xia, Wei Wang, William J. Britt, Christina Paulus, Michael Nevels, Min‐Hua Luo · 发表于：Journal of Virology · 年份：2018 · DOI：10.1128/jvi.00340-18 · 被引用次数：28 · 研究领域：Cytomegalovirus and herpesvirus research、CRISPR and Genetic Engineering、RNA regulation and disease

Human cytomegalovirus (HCMV) infections are a leading cause of brain damage, hearing loss, and other neurological disabilities in children. We report that the HCMV proteins known as IE1 and IE2 target expression of human SOX2, a central pluripotency-associated transcription factor that governs neural progenitor cell (NPC) fate and is required for normal brain development. Both during HCMV infection and when expressed alone, IE1 causes the loss of SOX2 from NPCs. IE1 mediates SOX2 depletion by targeting STAT3, a critical upstream regulator of SOX2 expression. Our findings reveal an unanticipated mechanism by which a common virus may cause damage to the developing nervous system and suggest novel targets for medical intervention.