Wednesday, 26 November 2014

Modeling JCV virus infection

Kondo Y, Windrem MS, Zou L, Chandler-Militello D, Schanz SJ, Auvergne RM, Betstadt SJ, Harrington AR, Johnson M, Kazarov A, Gorelik L, Goldman SA.Human glial chimeric mice reveal astrocytic dependence of JC virus infection. J Clin Invest. 2014 Nov . pii: 76629. doi: 10.1172/JCI76629. [Epub ahead of print]

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 (post-birth) immunodeficient (no effective immune system so it will not reject human cells) and myelin-deficient mice. The human cells then produce the myelin in the miceIntracerebral delivery (brain injection) of JCV resulted in infection and subsequent demyelination of these 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 antigens and exhibited death. Engraftment of human GPCs in normally myelinated and immunodeficient mice resulted in humanized white matter that had 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 oligodendroglial apoptosis. More broadly, this study provides a model by which to further assess the biology and treatment of human-specific gliotropic viruses.
Demyelination after JC virus has been mooted as a main problem in PML, however in this study they got a mouse and made it contain human glial cells and mylein and it suggests that infection of astrocytes is the main problem and that oligodendrocyte is a later casualty. This now gives a tool to hunt for treatments to JCV infection

3 comments:

  1. This could really be very important; if we will be able to fight JVC infection, it will means that one of the most important risk factor in highly effective Ms treatments will be extremely reduced.

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  2. MD, that's not an icosahedral jc virus, looks more like a gram negative bacterium with pili. If researchers can't distinguish a virus from a bacterium we're in trouble :-) Happy thanksgiving to all who celebrate with family and friends (maybe make a kidney pie in the shape of a turkey)

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    Replies
    1. Afraid we have to blame google images for this one, I have posted so many dull images of JC virus, I thought this picture was more interesting but just to please you for the holiday season I have changed it for the dull virus picture...hope you are satisfied.

      I suspect the virologist could tell the difference between an T cell rom a B cell.

      As is common, the picture does not always reflect the post, likewise I sometimes remove bits from the abstract because I can't be bothered or don't have the time to explain the content e.g. multivariate regression etc as it is irrelevant to post. If i do change anything it is in italics.

      Have a fun weekend and spare a through for those working whilst you tuck into your turkey.

      As to recognising virus from bacteria I can't recognise sense from nosense half- the time:-)

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