skip to main content
Ngôn ngữ:
Giới hạn tìm kiếm: Giới hạn tìm kiếm: Dạng tài nguyên Hiển thị kết quả với: Hiển thị kết quả với: Chỉ mục

Borna Disease Virus Phosphoprotein Impairs the Developmental Program Controlling Neurogenesis and Reduces Human GABAergic Neurogenesis (BDV Phosphoprotein Alters Human Neurogenesis)

Scordel, Chloé ; Huttin, Alexandra ; Cochet-Bernoin, Marielle ; Szelechowski, Marion ; Poulet, Aurélie ; Richardson, Jennifer ; Benchoua, Alexandra ; Gonzalez-Dunia, Daniel ; Eloit, Marc ; Coulpier, Muriel; Schwemmle, Martin (Editor)

2015, Vol.11(4), p.e1004859 [Tạp chí có phản biện]

ISSN: 1553-7366 ; E-ISSN: 1553-7374 ; DOI: 10.1371/journal.ppat.1004859

Toàn văn sẵn có

Trích dẫn Trích dẫn bởi
  • Nhan đề:
    Borna Disease Virus Phosphoprotein Impairs the Developmental Program Controlling Neurogenesis and Reduces Human GABAergic Neurogenesis (BDV Phosphoprotein Alters Human Neurogenesis)
  • Tác giả: Scordel, Chloé ; Huttin, Alexandra ; Cochet-Bernoin, Marielle ; Szelechowski, Marion ; Poulet, Aurélie ; Richardson, Jennifer ; Benchoua, Alexandra ; Gonzalez-Dunia, Daniel ; Eloit, Marc ; Coulpier, Muriel
  • Schwemmle, Martin (Editor)
  • Chủ đề: Research Article
  • Là 1 phần của: 2015, Vol.11(4), p.e1004859
  • Mô tả: It is well established that persistent viral infection may impair cellular function of specialized cells without overt damage. This concept, when applied to neurotropic viruses, may help to understand certain neurologic and neuropsychiatric diseases. Borna disease virus (BDV) is an excellent example of a persistent virus that targets the brain, impairs neural functions without cell lysis, and ultimately results in neurobehavioral disturbances. Recently, we have shown that BDV infects human neural progenitor cells (hNPCs) and impairs neurogenesis, revealing a new mechanism by which BDV may interfere with brain function. Here, we sought to identify the viral proteins and molecular pathways that are involved. Using lentiviral vectors for expression of the bdv-p and bdv-x viral genes, we demonstrate that the phosphoprotein P, but not the X protein, diminishes human neurogenesis and, more particularly, GABAergic neurogenesis. We further reveal a decrease in pro-neuronal factors known to be involved in neuronal differentiation ( ApoE , Noggin , TH and Scg10/Stathmin2 ), demonstrating that cellular dysfunction is associated with impairment of specific components of the molecular program that controls neurogenesis. Our findings thus provide the first evidence that a viral protein impairs GABAergic human neurogenesis, a process that is dysregulated in several neuropsychiatric disorders. They improve our understanding of the mechanisms by which a persistent virus may interfere with brain development and function in the adult. ; When a virus enters the brain, it most often induces inflammation, fever, and brain injury, all signs that are indicative of acute encephalitis. Under certain conditions, however, some neurotropic viruses may cause disease in a subtler manner. The Borna disease virus (BDV) is an excellent example of this second class of viruses, as it impairs neural function without cell lysis and induces neurobehavioral disturbances. Recently, we have shown that BDV infects human neural progenitor cells (hNPCs) and impairs neurogenesis, revealing a new mechanism by which BDV may interfere with brain function. In the present study, we identify that a singled-out BDV protein called P causes similar impairment of human neurogenesis, and further show that it leads to diminution in the genesis of a particular neuronal subtype, the GABAergic neurons. We have also found that the expression of several genes involved in the generation and the maturation of neurons is dysregulated by this viral protein, which strongly suggests their implication in P-induced impairment of GABAergic neurogenesis. This study is the first to demonstrate that a viral protein interferes with human GABAergic neurogenesis, a process that is frequently impaired in neuropsychiatric disorders. It may thus contribute to elucidating the molecular bases of psychiatric disorders.
  • Ngôn ngữ: English
  • Số nhận dạng: ISSN: 1553-7366 ; E-ISSN: 1553-7374 ; DOI: 10.1371/journal.ppat.1004859

Đang tìm Cơ sở dữ liệu bên ngoài...