Regulation of neurotropic herpesvirus productive infection and latency-reactivation cycle by glucocorticoid receptor and stress-induced transcription factors.

Neurotropic α-herpesvirinae subfamily members, herpes simplex virus type 1 (HSV-1) and bovine herpesvirus 1 (BoHV-1), are important viral pathogens in their respective hosts. Following acute infection on mucosal surfaces, these viruses establish life-long latency in neurons within trigeminal ganglia (TG) and central nervous system. Chronic or acute stress (physiological or psychological) increases the frequency of reactivation from latency, which leads to virus shedding, virus transmission, and recurrent disease.

A Pioneer Transcription Factor and Type I Nuclear Hormone Receptors Synergistically Activate the Bovine Herpesvirus 1 Infected Cell Protein 0 (ICP0) Early Promoter.

Following bovine herpesvirus 1 (BoHV-1) acute infection of ocular, oral, or nasal cavities, sensory neurons within trigeminal ganglia are an important site for latency. Stress, as mimicked by the synthetic corticosteroid dexamethasone, consistently induces reactivation from latency. Expression of two key viral transcriptional regulatory proteins, BoHV-1 infected cell protein 0 (bICP0) and bICP4, are regulated by sequences within the immediate early promoter (IEtu1).

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.

Pioneer transcription factors, progesterone receptor and Krüppel like transcription factor 4, cooperatively stimulate the bovine herpesvirus 1 ICP0 early promoter and productive late protein expression.

Bovine herpesvirus 1 (BoHV-1), including commercially available modified live vaccines, readily infect the fetus and ovaries, which can cause reproductive failure. The BoHV-1 latency-reactivation cycle in sensory neurons further complicates reproductive failure because progesterone sporadically induces reactivation from latency. The progesterone receptor (PR) and Krüppel-like transcription factor 15 (KLF15) cooperatively stimulate productive infection and the immediate early transcription unit 1 (IEtu1) promoter.

Two Pioneer Transcription Factors, Krüppel-Like Transcription Factor 4 and Glucocorticoid Receptor, Cooperatively Transactivate the Bovine Herpesvirus 1 ICP0 Early Promoter and Stimulate Productive Infection.

An important site for bovine herpesvirus 1 (BoHV-1) latency is sensory neurons within trigeminal ganglia (TG). The synthetic corticosteroid dexamethasone consistently induces BoHV-1 reactivation from latency. Expression of four Krüppel-like transcription factors (KLF), i.

Progesterone increases the incidence of bovine herpesvirus 1 reactivation from latency and stimulates productive infection.

Bovine herpesvirus 1 (BoHV-1), including modified live vaccines, can cause abortions in pregnant cows. Progesterone maintains pregnancy and promotes spermiogenesis and testosterone biosynthesis in males: furthermore, progesterone is a neuro-steroid. Recent published studies demonstrated progesterone stimulated the BoHV-1 immediate early transcription unit 1 (IEtu1) promoter, and two glucocorticoid receptor response elements within the promoter were required for progesterone mediated transactivation.

The Cellular Coactivator HCF-1 Is Required for Glucocorticoid Receptor-Mediated Transcription of Bovine Herpesvirus 1 Immediate Early Genes.

Following productive infection, bovine herpesvirus 1 (BoHV-1) establishes latency in sensory neurons. As in other alphaherpesviruses, expression of BoHV-1 immediate early (IE) genes is regulated by an enhancer complex containing the viral IE activator VP16, the cellular transcription factor Oct-1, and transcriptional coactivator HCF-1, which is assembled on an IE enhancer core element (TAATGARAT). Expression of the IE transcription unit that encodes the viral IE activators bICP0 and bICP4 may also be induced by the activated glucocorticoid receptor (GR) via two glucocorticoid response elements (GREs) located upstream of the enhancer core.

Combinatorial Effects of the Glucocorticoid Receptor and Krüppel-Like Transcription Factor 15 on Bovine Herpesvirus 1 Transcription and Productive Infection.

Bovine herpesvirus 1 (BoHV-1), an important bovine pathogen, establishes lifelong latency in sensory neurons. Latently infected calves consistently reactivate from latency following a single intravenous injection of the synthetic corticosteroid dexamethasone. The immediate early transcription unit 1 (IEtu1) promoter, which drives bovine ICP0 (bICP0) and bICP4 expression, is stimulated by dexamethasone because it contains two glucocorticoid receptor (GR) response elements (GREs).