HCMV Immediate Early Proteins Promote Lytic Infection and Reactivation in Monocytes

Like all herpesviruses, HCMV can establish a latent infection that persists throughout the lifetime of the host. The HCMV immediate early (IE) proteins, IE1 and IE2, are viewed as master regulators of HCMV infection and are commonly assumed to play pivotal roles in regulating the balance between latent and lytic infection, as their repression is a hallmark of latency.

However, it is still unclear whether their expression can indeed determine the establishment of productive infection and what are the functions, either related to viral gene expression or to cellular pathways, involved in this activity. Using THP1 monocytes, ectopically expressing the HCMV receptor, PDGFRα to boost viral entry, we show that overexpression of either IE1 or IE2 significantly enhances productive infection, illustrating their critical role in determining infection outcome.