Human cytomegalovirus infection dysregulates the localization and stability of nicd1 and jag1 in neural progenitor cells
文献类型：期刊论文
| 作者 | Li, Xiao-Jun1; Liu, Xi-Juan1; Yang, Bo1; Fu, Ya-Ru1; Zhao, Fei1; Shen, Zhang-Zhou1; Miao, Ling-Feng1; Rayner, Simon1; Chavanas, Stephane2; Zhu, Hua3 |
| 刊名 | Journal of virology
 |
| 出版日期 | 2015-07-01 |
| 卷号 | 89期号:13页码:6792-6804 |
| ISSN号 | 0022-538X |
| DOI | 10.1128/jvi.00351-15 |
| 通讯作者 | Luo, min-hua(luomh@wh.iov.cn) |
| 英文摘要 | Human cytomegalovirus (hcmv) infection of the developing fetus frequently results in major neural developmental damage. in previous studies, hcmv was shown to downregulate neural progenitor/stem cell (npc) markers and induce abnormal differentiation. as notch signaling plays a vital role in the maintenance of stem cell status and is a switch that governs npc differentiation, the effect of hcmv infection on the notch signaling pathway in npcs was investigated. hcmv downregulated mrna levels of notch1 and its ligand, jag1, and reduced protein levels and altered the intracellular localization of jag1 and the intracellular effector form of notch1, nicd1. these effects required hcmv gene expression and appeared to be mediated through enhanced proteasomal degradation. transient expression of the viral tegument proteins of pp71 and ul26 reduced nicd1 and jag1 protein levels endogenously and exogenously. given the critical role of notch signaling in npc growth and differentiation, these findings reveal important mechanisms by which hcmv disturbs neural cell development in vitro. similar events in vivo may be associated with hcmv-mediated neuropathogenesis during congenital infection in the fetal brain. importance congenital human cytomegalovirus (hcmv) infection is the leading cause of birth defects that primarily manifest as neurological disabilities. neural progenitor cells (npcs), key players in fetal brain development, are the most susceptible cell type for hcmv infection in the fetal brain. studies have shown that npcs are fully permissive for hcmv infection, which causes neural cell loss and premature differentiation, thereby perturbing npc fate. elucidation of virus-host interactions that govern npc proliferation and differentiation is critical to understanding neuropathogenesis. the notch signaling pathway is critical for maintaining stem cell status and functions as a switch for differentiation of npcs. our investigation into the impact of hcmv infection on this pathway revealed that hcmv dysregulates notch signaling by altering expression of the notch ligand jag1, notch1, and its active effector in npcs. these results suggest a mechanism for the neuropathogenesis induced by hcmv infection that includes altered npc differentiation and proliferation. |
| WOS关键词 | NOTCH SIGNALING PATHWAY ; NF-KAPPA-B ; CONGENITAL CYTOMEGALOVIRUS ; LIGAND JAGGED1 ; NEURONAL DIFFERENTIATION ; TUMOR SUPPRESSORS ; PRECURSOR CELLS ; HEARING-LOSS ; STEM-CELLS ; HLA-DR |
| WOS研究方向 | Virology |
| WOS类目 | Virology |
| 语种 | 英语 |
| 出版者 | AMER SOC MICROBIOLOGY |
| WOS记录号 | WOS:000355593000023 |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2375183 |
| 专题 | 武汉病毒研究所 |
| 通讯作者 | Luo, Min-Hua |
| 作者单位 | 1.Chinese Acad Sci, Wuhan Inst Virol, CAS Ctr Excellence Brain Sci, State Key Lab Virol, Wuhan, Peoples R China 2.Fac Med Toulouse, INSERM, U563, F-31073 Toulouse, France 3.Rutgers State Univ, New Jersey Med Sch, Dept Microbiol Biochem & Mol Genet, Newark, NJ 07102 USA 4.Univ Alabama Birmingham, Sch Med, Dept Pediat, Birmingham, AL USA 5.Howard Univ, Coll Med, Dept Microbiol, Washington, DC USA 6.Virginia Commonwealth Univ, Sch Med, Dept Pediat, Richmond, VA USA |
| 推荐引用方式 GB/T 7714 | Li, Xiao-Jun,Liu, Xi-Juan,Yang, Bo,et al. Human cytomegalovirus infection dysregulates the localization and stability of nicd1 and jag1 in neural progenitor cells[J]. Journal of virology,2015,89(13):6792-6804. |
| APA | Li, Xiao-Jun.,Liu, Xi-Juan.,Yang, Bo.,Fu, Ya-Ru.,Zhao, Fei.,...&Luo, Min-Hua.(2015).Human cytomegalovirus infection dysregulates the localization and stability of nicd1 and jag1 in neural progenitor cells.Journal of virology,89(13),6792-6804. |
| MLA | Li, Xiao-Jun,et al."Human cytomegalovirus infection dysregulates the localization and stability of nicd1 and jag1 in neural progenitor cells".Journal of virology 89.13(2015):6792-6804. |
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来源：武汉病毒研究所
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