Peroxisome proliferator-activated receptor γ (PPARγ) activation: A key determinant of neuropathogeny during congenital infection by cytomegalovirus

Abstract

Congenital infection by human cytomegalovirus (HCMV) might result in permanent neurological sequelae, including sensorineural deafness, cerebral palsies or devastating neurodevelopmental abnormalities. We recently disclosed that Peroxisome ProliferatorActivated Receptor gamma (PPARg), a transcription factor of the nuclear receptor superfamily, is a key determinant of HCMV pathogenesis in developing brain. Using neural stem cells from human embryonic stem cells, we showed that HCMV infection strongly increases levels and activity of PPARg in NSCs. Further in vitro experiments showed that PPARg activity inhibits the neuronogenic differentiation of NSCs into neurons. Consistently, increased PPARg expression was found in brain section of fetuses infected by HCMV, but not in uninfected controls. In this commentary, we summarize and discuss our findings and the new insights they provide on the neuropathogenesis of HCMV congenital infection.

Neural Stem Cells: What Happens When They Go Viral?

“…During CMV infection, PPARγ levels are elevated in the fetal brain. In vitro studies showed that PPARγ expression increased in CMV-infected NSCs and is associated with less neuronal differentiation [ 85 , 98 ]. Treatment of CMV-infected NSCs with a PPARγ inhibitor rescued abnormal differentiation, demonstrating the potential of identifying druggable targets for restoring NSC function.…”