Bovine herpesvirus 1 (BoHV-1), an important bovine pathogen, establishes life-long
latency in sensory neurons within trigeminal ganglia (TG). Stress, as mimicked by the
synthetic corticosteroid dexamethasone, consistently induces reactivation in calves
latently infected with BoHV-1. Dexamethasone induces expression of several transcription
factors in TG neurons during early stages of reactivation, including Krüppel-like
transcription factors (KLF): KLF4, KLF6, KLF15, and promyelocytic leukemia zinc finger.
Furthermore, the glucocorticoid receptor (GR) is consistently detected in TG neurons
expressing viral regulatory proteins during reactivation from latency. The viral
immediate early transcription unit 1 (IEtu1) promoter that drives expression of two viral
transcription factors (bICP0 and bICP4) contains two GR response elements (GREs) and
is stimulated by DEX. KLF15 and the GR form a feed forward transcription loop that
synergistically stimulates productive infection and IEtu1 promoter activity. New studies
demonstrate the GR and KLF6 synergistically stimulate productive infection and IEtu1
promoter activity if the GREs are intact. Furthermore, the GR and KLF6 interact with
wild-type GREs within the IEtu1 promoter, but not GRE mutants. These studies suggest
that certain KLF family members and the GR can convert a silent viral genome in latently
infected neurons into an actively transcribing genome during reactivation from latency.