Cooperative activation of bovine herpesvirus 1 productive infection and viral regulatory promoters by androgen receptor and Krüppel-like transcription factors 4 and 15.

Bovine herpesvirus 1 (BoHV-1), a significant viral pathogen, establishes latency in sensory neurons. The viral genome contains more than 100 consensus glucocorticoid receptor (GR) regulatory elements (GREs): consequently, stress stimulates viral replication and reactivation from latency. The immediate early transcription unit 1 (IEtu1) and bICP0 early promoters are transactivated by GR and synthetic corticosteroid dexamethasone. The androgen receptor (AR), like GR, is a Type 1 nuclear hormone receptor that binds and stimulates certain promoters containing GREs. Consequently, we hypothesized AR and 5α-Dihydrotestosterone (DHT) stimulate productive infection and key viral promoters. New studies demonstrated AR, DHT, and Krüppel like transcription factor 4 (KLF4) cooperatively stimulated productive infection and bICP0 E promoter activity in mouse neuroblastoma cells (Neuro-2A). KLF15 also cooperated with AR and DHT to stimulate IEtu1 promoter activity. We suggest AR and testosterone increase the prevalence of virus in semen by stimulating viral gene expression and replication.