Independent Cis-Regulatory Modules within the Herpes Simplex Virus 1 Infected Cell Protein 0 (ICP0) Promoter Are Transactivated by Krüppel-like Factor 15 and Glucocorticoid Receptor
A corticosteroid antagonist impairs Herpes Simplex Virus 1 (HSV-1) productive infection and explant-induced reactivation from latency, suggesting corticosteroids and the glucocorticoid receptor (GR) mediate certain aspects of these complex virus–host interactions. GR-hormone complexes regulate trans...
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| Format: | Article |
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MDPI AG
2022-06-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/14/6/1284 |
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| author | Nishani Wijesekera Nicholas Hazell Clinton Jones |
| author_facet | Nishani Wijesekera Nicholas Hazell Clinton Jones |
| author_sort | Nishani Wijesekera |
| collection | DOAJ |
| description | A corticosteroid antagonist impairs Herpes Simplex Virus 1 (HSV-1) productive infection and explant-induced reactivation from latency, suggesting corticosteroids and the glucocorticoid receptor (GR) mediate certain aspects of these complex virus–host interactions. GR-hormone complexes regulate transcription positively and negatively, in part, by binding GR response elements (GREs). Recent studies revealed infected cell protein 0 (ICP0), ICP4, and ICP27 promoter/cis-regulatory modules (CRMs) are cooperatively transactivated by GR and Krüppel-like factor 15 (KLF15), which forms a feed-forward transcription loop. We hypothesized the ICP0 promoter contains independent CRMs that are transactivated by GR, KLF15, and the synthetic corticosteroid dexamethasone (DEX). This hypothesis is based on the finding that the ICP0 promoter contains multiple transcription factor binding sites, and GR and KLF15 cooperatively transactivate the full-length ICP0 promoter. ICP0 promoter sequences spanning −800 to −635 (fragment A) were efficiently transactivated by GR, KLF15, and DEX in monkey kidney cells (Vero), whereas GR and DEX significantly enhanced promoter activity in mouse neuroblastoma cells (Neuro-2A). Furthermore, ICP0 fragment B (−458 to −635) was efficiently transactivated by GR, KLF15, and DEX in Vero cells, but not Neuro-2A cells. Finally, fragment D (−232 to −24) was transactivated significantly in Vero cells by GR, KLF15, and DEX, whereas KLF15 and DEX were sufficient for transactivation in Neuro-2A cells. Collectively, these studies revealed efficient transactivation of three independent CRMs within the ICP0 promoter by GR, KLF15, and/or DEX. Finally, GC-rich sequences containing specificity protein 1 (Sp1) binding sites were essential for transactivation. |
| first_indexed | 2024-03-09T22:14:05Z |
| format | Article |
| id | doaj.art-32cdf867d7cd41f49b157ca38520eed0 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T22:14:05Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-32cdf867d7cd41f49b157ca38520eed02023-11-23T19:26:48ZengMDPI AGViruses1999-49152022-06-01146128410.3390/v14061284Independent Cis-Regulatory Modules within the Herpes Simplex Virus 1 Infected Cell Protein 0 (ICP0) Promoter Are Transactivated by Krüppel-like Factor 15 and Glucocorticoid ReceptorNishani Wijesekera0Nicholas Hazell1Clinton Jones2Department of Veterinary Pathobiology, College of Veterinary Medicine, Oklahoma State University, 208 N McFarland Street, RM 250 McElroy Hall, Stillwater, OK 74078, USAExperimental Pathology Program, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555, USADepartment of Veterinary Pathobiology, College of Veterinary Medicine, Oklahoma State University, 208 N McFarland Street, RM 250 McElroy Hall, Stillwater, OK 74078, USAA corticosteroid antagonist impairs Herpes Simplex Virus 1 (HSV-1) productive infection and explant-induced reactivation from latency, suggesting corticosteroids and the glucocorticoid receptor (GR) mediate certain aspects of these complex virus–host interactions. GR-hormone complexes regulate transcription positively and negatively, in part, by binding GR response elements (GREs). Recent studies revealed infected cell protein 0 (ICP0), ICP4, and ICP27 promoter/cis-regulatory modules (CRMs) are cooperatively transactivated by GR and Krüppel-like factor 15 (KLF15), which forms a feed-forward transcription loop. We hypothesized the ICP0 promoter contains independent CRMs that are transactivated by GR, KLF15, and the synthetic corticosteroid dexamethasone (DEX). This hypothesis is based on the finding that the ICP0 promoter contains multiple transcription factor binding sites, and GR and KLF15 cooperatively transactivate the full-length ICP0 promoter. ICP0 promoter sequences spanning −800 to −635 (fragment A) were efficiently transactivated by GR, KLF15, and DEX in monkey kidney cells (Vero), whereas GR and DEX significantly enhanced promoter activity in mouse neuroblastoma cells (Neuro-2A). Furthermore, ICP0 fragment B (−458 to −635) was efficiently transactivated by GR, KLF15, and DEX in Vero cells, but not Neuro-2A cells. Finally, fragment D (−232 to −24) was transactivated significantly in Vero cells by GR, KLF15, and DEX, whereas KLF15 and DEX were sufficient for transactivation in Neuro-2A cells. Collectively, these studies revealed efficient transactivation of three independent CRMs within the ICP0 promoter by GR, KLF15, and/or DEX. Finally, GC-rich sequences containing specificity protein 1 (Sp1) binding sites were essential for transactivation.https://www.mdpi.com/1999-4915/14/6/1284herpes simplex virus type 1 (HSV-1)infected cell protein 0 (ICP0) expressionstressKrüppel-like factor 15glucocorticoid receptor (GR) |
| spellingShingle | Nishani Wijesekera Nicholas Hazell Clinton Jones Independent Cis-Regulatory Modules within the Herpes Simplex Virus 1 Infected Cell Protein 0 (ICP0) Promoter Are Transactivated by Krüppel-like Factor 15 and Glucocorticoid Receptor Viruses herpes simplex virus type 1 (HSV-1) infected cell protein 0 (ICP0) expression stress Krüppel-like factor 15 glucocorticoid receptor (GR) |
| title | Independent Cis-Regulatory Modules within the Herpes Simplex Virus 1 Infected Cell Protein 0 (ICP0) Promoter Are Transactivated by Krüppel-like Factor 15 and Glucocorticoid Receptor |
| title_full | Independent Cis-Regulatory Modules within the Herpes Simplex Virus 1 Infected Cell Protein 0 (ICP0) Promoter Are Transactivated by Krüppel-like Factor 15 and Glucocorticoid Receptor |
| title_fullStr | Independent Cis-Regulatory Modules within the Herpes Simplex Virus 1 Infected Cell Protein 0 (ICP0) Promoter Are Transactivated by Krüppel-like Factor 15 and Glucocorticoid Receptor |
| title_full_unstemmed | Independent Cis-Regulatory Modules within the Herpes Simplex Virus 1 Infected Cell Protein 0 (ICP0) Promoter Are Transactivated by Krüppel-like Factor 15 and Glucocorticoid Receptor |
| title_short | Independent Cis-Regulatory Modules within the Herpes Simplex Virus 1 Infected Cell Protein 0 (ICP0) Promoter Are Transactivated by Krüppel-like Factor 15 and Glucocorticoid Receptor |
| title_sort | independent cis regulatory modules within the herpes simplex virus 1 infected cell protein 0 icp0 promoter are transactivated by kruppel like factor 15 and glucocorticoid receptor |
| topic | herpes simplex virus type 1 (HSV-1) infected cell protein 0 (ICP0) expression stress Krüppel-like factor 15 glucocorticoid receptor (GR) |
| url | https://www.mdpi.com/1999-4915/14/6/1284 |
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