Cytomegalovirus Infection Affects the Differentiation and Determines the Functionality of a Human Progenitor Neural...

Cytomegalovirus (CMV) is a leading cause of congenital infections and one of the most common causes of neurodevelopmental disabilities worldwide. Despite the critical consequences of CMV infection in the brain, little is known about the mechanisms of neuropathogenesis responsible for malformations and dysfunction in the central nervous system. Some reports point out the infection of neural precursor cells (NPCs) as a key element in this process; these cells show the greatest susceptibility to CMV in the developing brain. In order to further characterize how CMV perturbs NPCs properties, we investigated the effect of human CMV strain AD169 in the neural stem cell cycle, viability, phenotype, and function of hNS-1 cells (immortalized cell line of human fetal brain). Notably, both infected and non-infected cells undergo apoptosis, with CMV infection not inducing a higher rate of apoptosis compared to non-infected cells. Upon infection and induction of differentiation in hNS-1 cells, the transcriptional expression of the NMDA receptor and the astrocyte marker GFAP is significantly reduced. Immunofluorescence assays corroborate the inhibition of astrocyte differentiation by CMV infection, while differentiation to neurons remains unaffected. Furthermore, our study demonstrates that CMV-infected hNS-1 cells exhibit impaired responses to multiple agonists after differentiation, including purinergic and GABAergic neurotransmission. These observations shed light on the previously understudied aspect of human CMV's influence on NPCs' function, providing valuable insights into the intricate interplay between CMV and neural development.