Cytomegalovirus in the human dentate gyrus and its impact on neural progenitor cells: report of two cases.

Congenital cytomegalovirus (CMV) infection in the 2^nd and 3^rd trimester results in catastrophic CNS abnormalities. This susceptibility is thought to result from the high proportion of neural stem cells in the developing brain. In immunocompromised adults, CNS infection by CMV preferentially affects ependymal surfaces, from where it expands to involve the parenchyma. Experimental models of murine CMV infection demonstrate viral tropism for the dentate gyrus (DG) and subventricular zone, the areas in which adult neurogenesis occurs. We present two cases of CMV infection of the DG of immunocompromised allogeneic stem cell transplant recipients. Both cases showed CMV-positive neurons in the DG granular cell layer, as well as contiguous layers. The majority of infected cells contained Nissl substance and expressed nestin, glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), and neurofilament. These cases demonstrate that CMV infects the DG in humans. Co-expression of nestin and GFAP, indicative of early neurogenesis, is consistent with experimental models showing neural stem cells as the target of CMV, providing further histological evidence of neurogenesis in the human dentate. Finally, the cases suggest that CMV infection produces abnormal migration of newly formed neurons as evidenced by the finding of virally infected neurons in the molecular layer of the dentate.
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