The herpes simplex virus-1 transactivator infected cell protein-4 drives VEGF-A dependent neovascularization.
Herpes simplex virus-1 (HSV-1) causes lifelong infection affecting between 50 and 90% of the global population. In addition to causing dermal lesions, HSV-1 is a leading cause of blindness resulting from recurrent corneal infection. Corneal disease is characterized by loss of corneal immunologic pri...
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| Language: | English |
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Public Library of Science (PLoS)
2011-10-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1002278&type=printable |
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| author | Todd Wuest Min Zheng Stacey Efstathiou William P Halford Daniel J J Carr |
| author_facet | Todd Wuest Min Zheng Stacey Efstathiou William P Halford Daniel J J Carr |
| author_sort | Todd Wuest |
| collection | DOAJ |
| description | Herpes simplex virus-1 (HSV-1) causes lifelong infection affecting between 50 and 90% of the global population. In addition to causing dermal lesions, HSV-1 is a leading cause of blindness resulting from recurrent corneal infection. Corneal disease is characterized by loss of corneal immunologic privilege and extensive neovascularization driven by vascular endothelial growth factor-A (VEGF-A). In the current study, we identify HSV-1 infected cells as the dominant source of VEGF-A during acute infection, and VEGF-A transcription did not require TLR signaling or MAP kinase activation. Rather than being an innate response to the pathogen, VEGF-A transcription was directly activated by the HSV-1 encoded immediate early transcription factor, ICP4. ICP4 bound the proximal human VEGF-A promoter and was sufficient to promote transcription. Transcriptional activation also required cis GC-box elements common to the VEGF-A promoter and HSV-1 early genes. Our results suggest that the neovascularization characteristic of ocular HSV-1 disease is a direct result of HSV-1's major transcriptional regulator, ICP4, and similarities between the VEGF-A promoter and those of HSV-1 early genes. |
| format | Article |
| id | doaj-art-df28e100d7ec4b30acb80457fce929bf |
| institution | DOAJ |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2011-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-df28e100d7ec4b30acb80457fce929bf2025-08-20T03:10:22ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742011-10-01710e100227810.1371/journal.ppat.1002278The herpes simplex virus-1 transactivator infected cell protein-4 drives VEGF-A dependent neovascularization.Todd WuestMin ZhengStacey EfstathiouWilliam P HalfordDaniel J J CarrHerpes simplex virus-1 (HSV-1) causes lifelong infection affecting between 50 and 90% of the global population. In addition to causing dermal lesions, HSV-1 is a leading cause of blindness resulting from recurrent corneal infection. Corneal disease is characterized by loss of corneal immunologic privilege and extensive neovascularization driven by vascular endothelial growth factor-A (VEGF-A). In the current study, we identify HSV-1 infected cells as the dominant source of VEGF-A during acute infection, and VEGF-A transcription did not require TLR signaling or MAP kinase activation. Rather than being an innate response to the pathogen, VEGF-A transcription was directly activated by the HSV-1 encoded immediate early transcription factor, ICP4. ICP4 bound the proximal human VEGF-A promoter and was sufficient to promote transcription. Transcriptional activation also required cis GC-box elements common to the VEGF-A promoter and HSV-1 early genes. Our results suggest that the neovascularization characteristic of ocular HSV-1 disease is a direct result of HSV-1's major transcriptional regulator, ICP4, and similarities between the VEGF-A promoter and those of HSV-1 early genes.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1002278&type=printable |
| spellingShingle | Todd Wuest Min Zheng Stacey Efstathiou William P Halford Daniel J J Carr The herpes simplex virus-1 transactivator infected cell protein-4 drives VEGF-A dependent neovascularization. PLoS Pathogens |
| title | The herpes simplex virus-1 transactivator infected cell protein-4 drives VEGF-A dependent neovascularization. |
| title_full | The herpes simplex virus-1 transactivator infected cell protein-4 drives VEGF-A dependent neovascularization. |
| title_fullStr | The herpes simplex virus-1 transactivator infected cell protein-4 drives VEGF-A dependent neovascularization. |
| title_full_unstemmed | The herpes simplex virus-1 transactivator infected cell protein-4 drives VEGF-A dependent neovascularization. |
| title_short | The herpes simplex virus-1 transactivator infected cell protein-4 drives VEGF-A dependent neovascularization. |
| title_sort | herpes simplex virus 1 transactivator infected cell protein 4 drives vegf a dependent neovascularization |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1002278&type=printable |
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