Stress Induced Transcription Factors Transactivate the Herpes Simplex Virus 1 Infected Cell Protein 27 (ICP27) Transcriptional Enhancer

Following acute infection, herpes simplex virus 1 (HSV-1) establishes lifelong latency in neurons, including sensory neurons within trigeminal ganglia. During latency, lytic cycle viral gene expression is silenced. However, stressful stimuli can trigger reactivation from latency. The viral tegument...

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Autores principales:	Jeffery B. Ostler, Clinton Jones
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	herpes simplex virus 1 infected cell protein 27 (ICP27) promoter/enhancer glucocorticoid receptor (GR) Krüppel-like factor 15 (KLF15) cooperative transactivation Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/0a77aa421f484d1889f04ced4e16799a
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spelling	oai:doaj.org-article:0a77aa421f484d1889f04ced4e16799a2021-11-25T19:14:17ZStress Induced Transcription Factors Transactivate the Herpes Simplex Virus 1 Infected Cell Protein 27 (ICP27) Transcriptional Enhancer10.3390/v131122961999-4915https://doaj.org/article/0a77aa421f484d1889f04ced4e16799a2021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4915/13/11/2296https://doaj.org/toc/1999-4915Following acute infection, herpes simplex virus 1 (HSV-1) establishes lifelong latency in neurons, including sensory neurons within trigeminal ganglia. During latency, lytic cycle viral gene expression is silenced. However, stressful stimuli can trigger reactivation from latency. The viral tegument protein, VP-16, transactivates all immediate early (IE) promoters during productive infection. Conversely, cellular factors are expected to trigger viral gene expression during early stages of reactivation from latency and in non-neuronal cells that do not support high levels of productive infection. The glucocorticoid receptor (GR), synthetic corticosteroid dexamethasone, and certain stress-induced transcription factors cooperatively transactivate infected cell protein 0 (ICP0) and ICP4 promoters. Since ICP27 protein expression is required for productive infection, we hypothesized that the ICP27 promoter is transactivated by stress-induced transcription factors. New studies have demonstrated that ICP27 enhancer sequences were transactivated by GR and Krüppel-like factor 15 (KLF15). Mutation of a consensus Sp1 binding site within ICP27 enhancer sequences impaired transactivation by GR and KLF15. Chromatin immunoprecipitation studies have demonstrated that GR and KLF15 occupy ICP27 promoter sequences during productive infection. Cells transfected with an ICP27 enhancer fragment revealed the GR and KLF15 occupancy of ICP27 enhancer sequences required the intact Sp1 binding site. Notably, GR and KLF15 form a feed-forward transcription loop in response to stress, suggesting these cellular factors promote viral replication following stressful stimuli.Jeffery B. OstlerClinton JonesMDPI AGarticleherpes simplex virus 1infected cell protein 27 (ICP27) promoter/enhancerglucocorticoid receptor (GR)Krüppel-like factor 15 (KLF15)cooperative transactivationMicrobiologyQR1-502ENViruses, Vol 13, Iss 2296, p 2296 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	herpes simplex virus 1 infected cell protein 27 (ICP27) promoter/enhancer glucocorticoid receptor (GR) Krüppel-like factor 15 (KLF15) cooperative transactivation Microbiology QR1-502
spellingShingle	herpes simplex virus 1 infected cell protein 27 (ICP27) promoter/enhancer glucocorticoid receptor (GR) Krüppel-like factor 15 (KLF15) cooperative transactivation Microbiology QR1-502 Jeffery B. Ostler Clinton Jones Stress Induced Transcription Factors Transactivate the Herpes Simplex Virus 1 Infected Cell Protein 27 (ICP27) Transcriptional Enhancer
description	Following acute infection, herpes simplex virus 1 (HSV-1) establishes lifelong latency in neurons, including sensory neurons within trigeminal ganglia. During latency, lytic cycle viral gene expression is silenced. However, stressful stimuli can trigger reactivation from latency. The viral tegument protein, VP-16, transactivates all immediate early (IE) promoters during productive infection. Conversely, cellular factors are expected to trigger viral gene expression during early stages of reactivation from latency and in non-neuronal cells that do not support high levels of productive infection. The glucocorticoid receptor (GR), synthetic corticosteroid dexamethasone, and certain stress-induced transcription factors cooperatively transactivate infected cell protein 0 (ICP0) and ICP4 promoters. Since ICP27 protein expression is required for productive infection, we hypothesized that the ICP27 promoter is transactivated by stress-induced transcription factors. New studies have demonstrated that ICP27 enhancer sequences were transactivated by GR and Krüppel-like factor 15 (KLF15). Mutation of a consensus Sp1 binding site within ICP27 enhancer sequences impaired transactivation by GR and KLF15. Chromatin immunoprecipitation studies have demonstrated that GR and KLF15 occupy ICP27 promoter sequences during productive infection. Cells transfected with an ICP27 enhancer fragment revealed the GR and KLF15 occupancy of ICP27 enhancer sequences required the intact Sp1 binding site. Notably, GR and KLF15 form a feed-forward transcription loop in response to stress, suggesting these cellular factors promote viral replication following stressful stimuli.
format	article
author	Jeffery B. Ostler Clinton Jones
author_facet	Jeffery B. Ostler Clinton Jones
author_sort	Jeffery B. Ostler
title	Stress Induced Transcription Factors Transactivate the Herpes Simplex Virus 1 Infected Cell Protein 27 (ICP27) Transcriptional Enhancer
title_short	Stress Induced Transcription Factors Transactivate the Herpes Simplex Virus 1 Infected Cell Protein 27 (ICP27) Transcriptional Enhancer
title_full	Stress Induced Transcription Factors Transactivate the Herpes Simplex Virus 1 Infected Cell Protein 27 (ICP27) Transcriptional Enhancer
title_fullStr	Stress Induced Transcription Factors Transactivate the Herpes Simplex Virus 1 Infected Cell Protein 27 (ICP27) Transcriptional Enhancer
title_full_unstemmed	Stress Induced Transcription Factors Transactivate the Herpes Simplex Virus 1 Infected Cell Protein 27 (ICP27) Transcriptional Enhancer
title_sort	stress induced transcription factors transactivate the herpes simplex virus 1 infected cell protein 27 (icp27) transcriptional enhancer
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/0a77aa421f484d1889f04ced4e16799a
work_keys_str_mv	AT jefferybostler stressinducedtranscriptionfactorstransactivatetheherpessimplexvirus1infectedcellprotein27icp27transcriptionalenhancer AT clintonjones stressinducedtranscriptionfactorstransactivatetheherpessimplexvirus1infectedcellprotein27icp27transcriptionalenhancer
_version_	1718410135248830464

Stress Induced Transcription Factors Transactivate the Herpes Simplex Virus 1 Infected Cell Protein 27 (ICP27) Transcriptional Enhancer

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