Regulation of Krüppel-Like Factor 15 Expression by Herpes Simplex Virus Type 1 or Bovine Herpesvirus 1 Productive Infection
Expression of Krüppel-like factor 15 (KLF15), a stress-induced transcription factor, is induced during bovine herpesvirus 1 (BoHV-1) reactivation from latency, and KLF15 stimulates BoHV-1 replication. Transient transfection studies revealed that KLF15 and glucocorticoid receptor (GR) cooperatively t...
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| Format: | Article |
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MDPI AG
2021-06-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/13/6/1148 |
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| author | Fouad S. El-mayet Kelly S. Harrison Clinton Jones |
| author_facet | Fouad S. El-mayet Kelly S. Harrison Clinton Jones |
| author_sort | Fouad S. El-mayet |
| collection | DOAJ |
| description | Expression of Krüppel-like factor 15 (KLF15), a stress-induced transcription factor, is induced during bovine herpesvirus 1 (BoHV-1) reactivation from latency, and KLF15 stimulates BoHV-1 replication. Transient transfection studies revealed that KLF15 and glucocorticoid receptor (GR) cooperatively transactivate the BoHV-1-immediate-early transcription unit 1 (IEtu1), herpes simplex virus type 1 (HSV-1) infected cell protein 0 (ICP0), and ICP4 promoters. The IEtu1 promoter drives expression of bICP0 and bICP4, two key BoHV-1 transcriptional regulatory proteins. Based on these studies, we hypothesized infection is a stressful stimulus that increases KLF15 expression and enhances productive infection. New studies demonstrated that silencing KLF15 impaired HSV-1 productive infection, and KLF15 steady-state protein levels were increased at late stages of productive infection. KLF15 was primarily localized to the nucleus following infection of cultured cells with HSV-1, but not BoHV-1. When cells were transfected with a KLF15 promoter construct and then infected with HSV-1, promoter activity was significantly increased. The ICP0 gene, and to a lesser extent, bICP0 transactivated the KLF15 promoter in the absence of other viral proteins. In contrast, BoHV-1 or HSV-1 encoded VP16 had no effect on KLF15 promoter activity. Collectively, these studies revealed that HSV-1 and BoHV-1 productive infection increased KLF15 steady-state protein levels, which correlated with increased virus production. |
| first_indexed | 2024-03-10T10:23:42Z |
| format | Article |
| id | doaj.art-abdb4353ef494607a8d10a74a973b924 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T10:23:42Z |
| publishDate | 2021-06-01 |
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| record_format | Article |
| series | Viruses |
| spelling | doaj.art-abdb4353ef494607a8d10a74a973b9242023-11-22T00:12:51ZengMDPI AGViruses1999-49152021-06-01136114810.3390/v13061148Regulation of Krüppel-Like Factor 15 Expression by Herpes Simplex Virus Type 1 or Bovine Herpesvirus 1 Productive InfectionFouad S. El-mayet0Kelly S. Harrison1Clinton Jones2Department of Veterinary Pathobiology, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078, USADepartment of Veterinary Pathobiology, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078, USADepartment of Veterinary Pathobiology, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078, USAExpression of Krüppel-like factor 15 (KLF15), a stress-induced transcription factor, is induced during bovine herpesvirus 1 (BoHV-1) reactivation from latency, and KLF15 stimulates BoHV-1 replication. Transient transfection studies revealed that KLF15 and glucocorticoid receptor (GR) cooperatively transactivate the BoHV-1-immediate-early transcription unit 1 (IEtu1), herpes simplex virus type 1 (HSV-1) infected cell protein 0 (ICP0), and ICP4 promoters. The IEtu1 promoter drives expression of bICP0 and bICP4, two key BoHV-1 transcriptional regulatory proteins. Based on these studies, we hypothesized infection is a stressful stimulus that increases KLF15 expression and enhances productive infection. New studies demonstrated that silencing KLF15 impaired HSV-1 productive infection, and KLF15 steady-state protein levels were increased at late stages of productive infection. KLF15 was primarily localized to the nucleus following infection of cultured cells with HSV-1, but not BoHV-1. When cells were transfected with a KLF15 promoter construct and then infected with HSV-1, promoter activity was significantly increased. The ICP0 gene, and to a lesser extent, bICP0 transactivated the KLF15 promoter in the absence of other viral proteins. In contrast, BoHV-1 or HSV-1 encoded VP16 had no effect on KLF15 promoter activity. Collectively, these studies revealed that HSV-1 and BoHV-1 productive infection increased KLF15 steady-state protein levels, which correlated with increased virus production.https://www.mdpi.com/1999-4915/13/6/1148herpes simplex virus type 1 (HSV-1)bovine herpesvirus 1 (BoHV-1)Krüppel-like factor 15 (KLF15)infected cell protein 0 (ICP0)BoHV-1 ICP0 (bICP0) |
| spellingShingle | Fouad S. El-mayet Kelly S. Harrison Clinton Jones Regulation of Krüppel-Like Factor 15 Expression by Herpes Simplex Virus Type 1 or Bovine Herpesvirus 1 Productive Infection Viruses herpes simplex virus type 1 (HSV-1) bovine herpesvirus 1 (BoHV-1) Krüppel-like factor 15 (KLF15) infected cell protein 0 (ICP0) BoHV-1 ICP0 (bICP0) |
| title | Regulation of Krüppel-Like Factor 15 Expression by Herpes Simplex Virus Type 1 or Bovine Herpesvirus 1 Productive Infection |
| title_full | Regulation of Krüppel-Like Factor 15 Expression by Herpes Simplex Virus Type 1 or Bovine Herpesvirus 1 Productive Infection |
| title_fullStr | Regulation of Krüppel-Like Factor 15 Expression by Herpes Simplex Virus Type 1 or Bovine Herpesvirus 1 Productive Infection |
| title_full_unstemmed | Regulation of Krüppel-Like Factor 15 Expression by Herpes Simplex Virus Type 1 or Bovine Herpesvirus 1 Productive Infection |
| title_short | Regulation of Krüppel-Like Factor 15 Expression by Herpes Simplex Virus Type 1 or Bovine Herpesvirus 1 Productive Infection |
| title_sort | regulation of kruppel like factor 15 expression by herpes simplex virus type 1 or bovine herpesvirus 1 productive infection |
| topic | herpes simplex virus type 1 (HSV-1) bovine herpesvirus 1 (BoHV-1) Krüppel-like factor 15 (KLF15) infected cell protein 0 (ICP0) BoHV-1 ICP0 (bICP0) |
| url | https://www.mdpi.com/1999-4915/13/6/1148 |
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