Activation of the glucocorticoid receptor by dexamethasone enhances BHV‐1 productive infection

Abstract

Sensory neurons in trigeminal ganglia are the primary site for bovine herpes virus‐1 (BHV‐1) latency. Following stress, glucocorticoid levels increase leading to reactivation of BHV‐1 from latency. An IV injection of the synthetic glucocorticoid dexamethasone (DEX) to latently infected calves consistently induces reactivation. A recent study showed that DEX treatment stimulates expression of host cell genes which indirectly leads to activation of lytic cycle viral genes and enhanced productive infection. DEX functions primarily by agonizing the glucocorticoid receptor (GR). The BHV‐1 genome contains numerous GR consensus sequences suggesting that DEX‐activated GR can directly transactivate viral genes. This study investigated the effect of DEX and GR on BHV‐1 productive infection in vitro. When GR was over expressed in the absence of DEX, the effect on BHV‐1 productive infection was insignificant. In the presence of DEX, GR over expression enhanced productive infection 3‐fold. These studies suggest that DEX‐activated GR stimulates reactivation from latency by activating cellular transcription factors and/or signaling pathways. Conversely, DEX may directly stimulate reactivation from latency by binding to viral promoters and inducing lytic cycle viral gene expression in a small subset of latently infected neurons. This publication was funded by NIH grant 5P20RR016469 and NIGMS grant 8P20GM103427.