Human cytomegalovirus infection impairs axon formation via repressing glycogen synthase kinase-3β activity-mediated adenosine triphosphate synthesis

Human cytomegalovirus (HCMV)has a global distribution and is highly prevalent. HCMV infection has been recognized as a major contributor to neural development abnormalities in embryos and children. However, the underlying mechanisms by which HCMV infection leads to neurological diseases remain incompletely understood. Our study showed that HCMV inhibits neural cell differentiation by affecting the production of adenosine triphosphate (ATP) during neural differentiation. In this work, we found that HCMV infection interferes with the neural differentiation of stem cells from human exfoliated deciduous teeth (SHEDs)and human neuroblastoma cell line (SH-SY5Ys), affects the expression of neural cell markers, and inhibits the axon formation of neural cells. Under neurogenic inductive conditions, HCMV infection of SHEDs and SH-SY5Ys caused an increase in Glycogen synthase kinase-3β(GSK-3β) phosphorylation level and a decrease in GSK-3β phosphatase activity. HCMV infection was shown to inhibits GSK-3β activity, suppresses the level of mitochondrial oxidative phosphorylation in cells, reduces ATP production, impedes energy supply during neural differentiation, and inhibits neural differentiation. Our study sheds light on a molecular mechanism by which crosstalk between protein phosphorylation and oxidative phosphorylation links HCMV infection and neural differentiation and raises a potential strategy for the therapy of congenital HCMV infection. RNA-seq of human SHsy5y in control and experiment group of SHsy5y and SHsy5y_infection