Human glial chimeras may have applications beyond that of modeling the species-specific role of human glia in neurological function and dysfunction. In particular, these mice may permit us to better assess the biology of human-selective infectious and inflammatory diseases of the CNS. For instance, a number of pathogenic viruses of the human brain are gliotrophic, and some are specifically human in their species-selectivity. Viruses such as the JCV polyomavirus, the cause of progressive multifocal leukoencephalopathy (PML), and human herpesvirtus-6, another prominent viral encephalitis of immunocompromised individuals, have never been amenable to experimental study in vivo, since these are human glial-specific pathogens(Haley and Atwood 2014). On that basis, we asked whether human glial chimerization might permit these animals to be infected with human gliotrophic viruses in vivo, and if so whether these infected human glial chimeras might develop pathology replicating that of humans. By neonatally engrafting immunodeficient myelin-deficient rag2−/− x shi/shi mice with hGPCs, we established mice with a fully humanized white matter, which were then infected by intracerebral injection of JCV (Kondo et al. 2014). Within several weeks thereafter, the JCV-infected mice manifested oligodendrocytic loss with demyelination and astroglial proliferation, replicating thereby the cardinal features of human PML (Figure 5).
