Inhibition of MAPK signaling suppresses cytomegalovirus reactivation in CD34+ Kasumi-3 cells

Reactivation of latent human cytomegalovirus (CMV) can lead to severe complications in individuals with dysregulated immune systems. While antiviral therapies for CMV are approved, these compounds are limited by their toxicity and inability to specifically target the latent reservoir or prevent reactivation. Herein we show that CMV reactivation in Kasumi-3 cells, a CD34⁺ hematopoietic cell line, requires mitogen-activated protein kinase (MAPK) activation. Importantly, pharmacological inhibition of the MAPK signaling pathway, including MEK and ERK, restricts viral reactivation in Kasumi-3 cells. In sum, our findings show MEK-ERK signaling is critical for CMV reactivation, revealing a potential avenue for therapeutic intervention to prevent viral reactivation and downstream pathogenesis that is often detrimental for immunosuppressed and immunocompromised patients.