Human Cytomegalovirus Immediate Early 1 Protein Causes Loss of SOX2 from Neural Progenitor Cells by Trapping Unphosphorylated STAT3 in the Nucleus
文献类型：期刊论文
| 作者 | Luo, Min-Hua7,8,9; Nevels, Michael1; Paulus, Christina1,6; Britt, William J.2; Wang, Wei3; Xia, Hui-Min7; Jiang, Man4,5; Harwardt, Thomas6; Ye, Han-Qing9; Yang, Bo9 |
| 刊名 | JOURNAL OF VIROLOGY
 |
| 出版日期 | 2018-09-01 |
| 卷号 | 92期号:17页码:18 |
| 关键词 | HCMV IE1 neural progenitor cells SOX2 STAT3 |
| ISSN号 | 0022-538X |
| DOI | 10.1128/JVI.00340-18 |
| 英文摘要 | The mechanisms underlying neurodevelopmental damage caused by virus infections remain poorly defined. Congenital human cytomegalovirus (HCMV) infection is the leading cause of fetal brain development disorders. Previous work has linked HCMV infection to perturbations of neural cell fate, including premature differentiation of neural progenitor cells (NPCs). Here, we show that HCMV infection of NPCs results in loss of the SOX2 protein, a key pluripotency-associated transcription factor. SOX2 depletion maps to the HCMV major immediate early (IE) transcription unit and is individually mediated by the IE1 and IE2 proteins. IE1 causes SOX2 downregulation by promoting the nuclear accumulation and inhibiting the phosphorylation of STAT3, a transcriptional activator of SOX2 expression. Deranged signaling resulting in depletion of a critical stem cell protein is an unanticipated mechanism by which the viral major IE proteins may contribute to brain development disorders caused by congenital HCMV infection. IMPORTANCE 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. |
| 资助项目 | Ministry of Science and Technology of China (National Program on Key Basic Research Project)[2015CB755600] ; National Natural Science Foundation of China[81620108021] ; National Natural Science Foundation of China[31170155] ; National Natural Science Foundation of China[81427801] ; Sino-Africa Joint Research Centre[SAJC201605] ; seed grant from the University of Idaho[YDP-764] ; Wellcome Trust Institutional Strategic Support Fund ; Medical Research Council[MR/P022146/1] ; Tenovus Scotland[T15/38] ; Deutsche Forschungsgemeinschaft[PA 815/2-1] |
| WOS研究方向 | Virology |
| 语种 | 英语 |
| WOS记录号 | WOS:000443012300005 |
| 出版者 | AMER SOC MICROBIOLOGY |
| 源URL | [http://202.127.146.157/handle/2RYDP1HH/5688]  |
| 专题 | 中国科学院武汉植物园 |
| 通讯作者 | Luo, Min-Hua; Nevels, Michael |
| 作者单位 | 1.Univ St Andrews, Biomed Sci Res Complex, St Andrews, Fife, Scotland 2.Univ Alabama Birmingham, Sch Med, Dept Pediat, Birmingham, AL USA 3.Cent S Univ, Xiangya Hosp 3, Changsha, Hunan, Peoples R China 4.Huazhong Univ Sci & Technol, Tongji Med Coll, Wuhan, Hubei, Peoples R China 5.Huazhong Univ Sci & Technol, Sch Basic Med, Dept Physiol, Wuhan, Hubei, Peoples R China 6.Univ Regensburg, Inst Med Microbiol & Hyg, Regensburg, Germany 7.Guangzhou Med Univ, Guangzhou Women & Childrens Med Ctr, Guangzhou, Guangdong, Peoples R China 8.Univ Chinese Acad Sci, Beijing, Peoples R China 9.Chinese Acad Sci, Wuhan Inst Virol, Ctr Excellence Brain Sci & Intelligence Technol, State Key Lab Virol, Wuhan, Hubei, Peoples R China |
| 推荐引用方式 GB/T 7714 | Luo, Min-Hua,Nevels, Michael,Paulus, Christina,et al. Human Cytomegalovirus Immediate Early 1 Protein Causes Loss of SOX2 from Neural Progenitor Cells by Trapping Unphosphorylated STAT3 in the Nucleus[J]. JOURNAL OF VIROLOGY,2018,92(17):18. |
| APA | Luo, Min-Hua.,Nevels, Michael.,Paulus, Christina.,Britt, William J..,Wang, Wei.,...&Wu, Cong-Cong.(2018).Human Cytomegalovirus Immediate Early 1 Protein Causes Loss of SOX2 from Neural Progenitor Cells by Trapping Unphosphorylated STAT3 in the Nucleus.JOURNAL OF VIROLOGY,92(17),18. |
| MLA | Luo, Min-Hua,et al."Human Cytomegalovirus Immediate Early 1 Protein Causes Loss of SOX2 from Neural Progenitor Cells by Trapping Unphosphorylated STAT3 in the Nucleus".JOURNAL OF VIROLOGY 92.17(2018):18. |
入库方式： OAI收割
来源：武汉植物园
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