Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact

Submit a comment

Human glial chimeric mice reveal astrocytic dependence of JC virus infection
Yoichi Kondo, … , Leonid Gorelik, Steven A. Goldman
Yoichi Kondo, … , Leonid Gorelik, Steven A. Goldman
Published November 17, 2014
Citation Information: J Clin Invest. 2014;124(12):5323-5336. https://doi.org/10.1172/JCI76629.
View: Text | PDF
Research Article Article has an altmetric score of 29

Human glial chimeric mice reveal astrocytic dependence of JC virus infection

  • Text
  • PDF
Abstract

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease triggered by infection with the human gliotropic JC virus (JCV). Due to the human-selective nature of the virus, there are no animal models available to investigate JCV pathogenesis. To address this issue, we developed mice with humanized white matter by engrafting human glial progenitor cells (GPCs) into neonatal immunodeficient and myelin-deficient mice. Intracerebral delivery of JCV resulted in infection and subsequent demyelination of these chimeric mice. Human GPCs and astrocytes were infected more readily than oligodendrocytes, and viral replication was noted primarily in human astrocytes and GPCs rather than oligodendrocytes, which instead expressed early viral T antigens and exhibited apoptotic death. Engraftment of human GPCs in normally myelinated and immunodeficient mice resulted in humanized white matter that was chimeric for human astrocytes and GPCs. JCV effectively propagated in these mice, which indicates that astroglial infection is sufficient for JCV spread. Sequencing revealed progressive mutation of the JCV capsid protein VP1 after infection, suggesting that PML may evolve with active infection. These results indicate that the principal CNS targets for JCV infection are astrocytes and GPCs and that infection is associated with progressive mutation, while demyelination is a secondary occurrence, following T antigen–triggered oligodendroglial apoptosis. More broadly, this study provides a model by which to further assess the biology and treatment of human-specific gliotropic viruses.

Authors

Yoichi Kondo, Martha S. Windrem, Lisa Zou, Devin Chandler-Militello, Steven J. Schanz, Romane M. Auvergne, Sarah J. Betstadt, Amy R. Harrington, Mahlon Johnson, Alexander Kazarov, Leonid Gorelik, Steven A. Goldman

×

Guidelines

The Editorial Board will only consider comments that are deemed relevant and of interest to readers. The Journal will not post data that have not been subjected to peer review; or a comment that is essentially a reiteration of another comment.

  • Comments appear on the Journal’s website and are linked from the original article’s web page.
  • Authors are notified by email if their comments are posted.
  • The Journal reserves the right to edit comments for length and clarity.
  • No appeals will be considered.
  • Comments are not indexed in PubMed.

Specific requirements

  • Maximum length, 400 words
  • Entered as plain text or HTML
  • Author’s name and email address, to be posted with the comment
  • Declaration of all potential conflicts of interest (even if these are not ultimately posted); see the Journal’s conflict-of-interest policy
  • Comments may not include figures
This field is required
This field is required
This field is required
This field is required
This field is required
This field is required
Rich Text Editor, eletter_body
Editor toolbarsClipboard/Undo CutKeyboard shortcut Ctrl+X CopyKeyboard shortcut Ctrl+C PasteKeyboard shortcut Ctrl+V Paste as plain textKeyboard shortcut Ctrl+Alt+Shift+V Paste from Word UndoKeyboard shortcut Ctrl+Z RedoKeyboard shortcut Ctrl+YEditing Find Replace Select All Spell Check As You TypeLinks LinkKeyboard shortcut Ctrl+K Unlink AnchorForms Form Checkbox Radio Button Text Field Textarea Selection Field Button Image Button Hidden FieldTools Maximize Show BlocksDocument Source Save New Page Preview Print TemplatesBasic Styles BoldKeyboard shortcut Ctrl+B ItalicKeyboard shortcut Ctrl+I UnderlineKeyboard shortcut Ctrl+U Strikethrough Subscript Superscript Copy FormattingKeyboard shortcut Ctrl+Shift+C Remove FormatParagraph Insert/Remove Numbered List Insert/Remove Bulleted List Decrease Indent Increase Indent Block Quote Create Div Container Align Left Center Align Right Justify Text direction from left to right Text direction from right to left Set languageStylesStylesStylesFormatFormatFontFontSizeSizeColors Text Color Background Color
Press ALT 0 for help
◢Elements path 

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Blogged by 2
Posted by 4 X users
Referenced in 1 patents
On 2 Facebook pages
Mentioned in 8 Google+ posts
79 readers on Mendeley
See more details