Human brain organoid to study JC virus infection
2022
Johns Hopkins University, Baltimore, USA
Progressive multifocal leukoencephalopathy (PML) is a common neurological complication in immunocompromised patients. PML is caused by JC virus (JCV), a neurotropic DNA polyomavirus that infects oligodendrocytes and astrocytes, causing inflammation and demyelination leading to neurologic dysfunction. The pathogenesis of PML is poorly understood to date, except that the virus infects only human cells.
Here, using human induced pluripotent stem cells (iPSCs), organotypic models were generated with neurons, astrocytes, and oligodendrocytes that mimic aspects of the human brain environment. These brain organoids were then infected with JCV strain MAD4 or CSF from a patient with PML.
At 1, 2, and 3 weeks after exposure, the organoids were examined for signs of infection by qPCR, immunofluorescence, and electron microscopy. The researchers detected JCV infection of oligodendrocytes, astrocytes, and media of both JCV-MAD4 strain-exposed and PML-liquor-exposed brain organoids. In contrast, no evidence of neuronal infection was detected. In conclusion, the brain organoid model of JCV infection represents a human model suitable for studying the mechanisms of JCV infection and the pathogenesis of PML and may facilitate the exploration of therapeutic approaches.
A human-derived 3D brain organoid model to study JC virus infection
Carlos A. Pardo
Added on: 04-14-2022
[1] https://link.springer.com/article/10.1007/s13365-022-01062-7
