Synergistic Activation of Bovine Herpesvirus 1 Productive Infection and Viral Regulatory Promoters by the Progesterone Receptor and Krüppel-Like Transcription Factor 15.
Animals
Binding Sites
Cattle
Cattle Diseases
/ virology
Gene Expression Regulation, Viral
Herpesviridae Infections
/ metabolism
Herpesvirus 1, Bovine
/ genetics
Kruppel-Like Transcription Factors
/ metabolism
Progesterone
/ pharmacology
Promoter Regions, Genetic
Receptors, Glucocorticoid
/ metabolism
Response Elements
Viral Proteins
/ genetics
Virus Replication
BoHV-1
productive infection
progesterone receptor
regulation of gene expression
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
01 01 2019
01 01 2019
Historique:
received:
31
08
2018
accepted:
03
10
2018
pubmed:
12
10
2018
medline:
1
10
2019
entrez:
12
10
2018
Statut:
epublish
Résumé
Bovine herpesvirus 1 (BoHV-1), including modified live vaccines, readily infects the fetus and ovaries, which can lead to reproductive failure. The BoHV-1 latency reactivation cycle in sensory neurons may further complicate reproductive failure in pregnant cows. The immediate early transcription unit 1 (IEtu1) promoter drives expression of important viral transcriptional regulators (bICP0 and bICP4). This promoter contains two functional glucocorticoid receptor (GR) response elements (GREs) that have the potential to stimulate productive infection following stressful stimuli. Since progesterone and the progesterone receptor (PR) can activate many GREs, we hypothesized that the PR and/or progesterone regulates productive infection and viral transcription. New studies demonstrated that progesterone stimulated productive infection. Additional studies revealed the PR and Krüppel-like transcription factor 15 (KLF15) cooperated to stimulate productive infection and IEtu1 promoter activity. IEtu1 promoter activation required both GREs, which correlated with the ability of the PR to interact with wild-type (wt) GREs but not mutant GREs. KLF15 also cooperated with the PR to transactivate the bICP0 early promoter, a promoter that maintains bICP0 protein expression during productive infection. Intergenic viral DNA fragments (less than 400 bp) containing two GREs and putative KLF binding sites present within genes encoding unique long 52 (UL-52; component of DNA primase/helicase complex), Circ, bICP4, and IEtu2 were stimulated by KLF15 and the PR more than 10-fold, suggesting that additional viral promoters are activated by these transcription factors. Collectively, these studies suggest progesterone and the PR promote BoHV-1 spread to reproductive tissues, thus increasing the incidence of reproductive failure.
Identifiants
pubmed: 30305353
pii: JVI.01519-18
doi: 10.1128/JVI.01519-18
pmc: PMC6288325
pii:
doi:
Substances chimiques
Kruppel-Like Transcription Factors
0
Receptors, Glucocorticoid
0
Viral Proteins
0
Progesterone
4G7DS2Q64Y
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIGMS NIH HHS
ID : P20 GM103648
Pays : United States
Informations de copyright
Copyright © 2018 American Society for Microbiology.
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