Infected T98G glioblastoma cells support human cytomegalovirus reactivation from latency

T98G cells have been demonstrated to support the long-term maintenance of the human cytomegalovirus (HCMV) genome without releasing infectious viruses. However, it remains uncertain whether these viral genomes can be reactivated. To explore this, a recombinant HCMV (rHCMV) containing a GFP gene was used to infect T98G cells, and the infected cells that did not produce Dibutyryl-cAMP infectious viruses were termed T98G-LrV. Following treatment with dibutyryl cAMP and IBMX (cAMP/IBMX), several events were observed, including an increase in GFP signal, viral genome replication, expression of lytic genes, and the release of infectious viruses. These findings suggest that HCMV can be reactivated from a latent state in T98G-LrV cells. Mechanistically, this reactivation, induced by cAMP/IBMX, was linked to the PKA-CREB signaling pathway. These results confirm that HCMV remains latent in T98G-LrV cells and can be reactivated. The T98G-LrV cells provide a valuable model for studying the mechanisms of HCMV reactivation from latency in neural cells.