Central nervous system (CNS) dysfunction caused by neurovirulent influenza viruses is a dreaded complication of
infection, and may play a role in some neurodegenerative conditions, such as Parkinson-like diseases and
encephalitis lethargica. Although
CNS infection by highly pathogenic H5N1 virus has been demonstrated, it is unknown whether H5N1 infects neural progenitor cells, nor whether such
infection plays a role in the
neuroinflammation and neurodegeneration. To pursue this question, we infected human neural progenitor cells (hNPCs) differentiated from human embryonic stem cells in vitro with H5N1 virus, and studied the resulting cytopathology,
cytokine expression, and genes involved in the differentiation. Human embryonic stem cells (BG01) were maintained and differentiated into the neural progenitors, and then infected by H5N1 virus (A/Chicken/Thailand/CUK2/04) at a multiplicity of
infection of 1. At 6, 24, 48, and 72 hours post-
infection (hpi), cytopathic effects were observed. Then cells were characterized by immunofluorescence and electron microscopy, supernatants quantified for virus titers, and sampled cells studied for candidate genes.The hNPCs were susceptible to H5N1 virus
infection as determined by morphological observation and immunofluorescence. The
infection was characterized by a significant up-regulation of TNF-α gene expression, while expressions of IFN-α2, IFN-β1, IFN-γ and
IL-6 remained unchanged compared to mock-infected controls. Moreover, H5N1
infection did not appear to alter expression of neuronal and astrocytic markers of hNPCs, such as β-III
tubulin and GFAP, respectively. The results indicate that hNPCs support H5N1 virus
infection and may play a role in the
neuroinflammation during acute
viral encephalitis.