Role of interferon regulatory factor 7 in corneal endothelial cells after HSV-1 infection
Abstract Viral infections of the cornea including herpes simplex virus 1 (HSV-1) cause visual morbidity, and the corneal endothelial cell damage leads to significant visual impairment. Interferon regulatory factor 7 (IRF7) has been identified as a significant regulator in corneal endothelial cells a...
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doaj-d525e5f2a6074af79da33093be0a70dc2021-08-15T11:25:40ZengNature Publishing GroupScientific Reports2045-23222021-08-0111111110.1038/s41598-021-95823-9Role of interferon regulatory factor 7 in corneal endothelial cells after HSV-1 infectionFumie Ohtani0Dai Miyazaki1Yumiko Shimizu2Tomoko Haruki3Satoru Yamagami4Yoshitsugu Inoue5Department of Ophthalmology, Tottori UniversityDepartment of Ophthalmology, Tottori UniversityDepartment of Ophthalmology, Tottori UniversityDepartment of Ophthalmology, Tottori UniversityDepartment of Ophthalmology, Nihon University School of MedicineDepartment of Ophthalmology, Tottori UniversityAbstract Viral infections of the cornea including herpes simplex virus 1 (HSV-1) cause visual morbidity, and the corneal endothelial cell damage leads to significant visual impairment. Interferon regulatory factor 7 (IRF7) has been identified as a significant regulator in corneal endothelial cells after an HSV-1 infection. To examine the role played by IRF7, the DNA binding domain (DBD) of IRF7 of human corneal endothelial cells (HCEn) was disrupted. An RNAi inhibition of IRF7 and IRF7 DBD disruption (IRF7 ∆DBD) led to an impairment of IFN-β production. Impaired IFN-β production by IRF7 ∆DBD was regained by IRF7 DNA transfection. Transcriptional network analysis indicated that IRF7 plays a role in antigen presentation function of corneal endothelial cells. When the antigen presentation activity of HCEn cells were examined for priming of memory CD8 T cells, IRF7 disruption abolished the anti-viral cytotoxic T lymphocyte (CTL) response which was dependent on the major histocompatibility complex (MHC) class I. To further examine the roles played by IRF7 in CTL induction as acquired immunity, the contribution of IRF7 to MHC class I-mediated antigen presentation was assessed. Analysis of IRF7 ∆DBD cells indicated that IRF7 played an unrecognized role in MHC class I induction, and the viral infection induced-MHC class I induction was abolished by IRF7 disruption. Collectively, the IRF7 in corneal endothelial cells not only contributed to type I IFN response, but also to the mediation of viral infection-induced MHC class I upregulation and priming of CD8 arm of acquired immunity.https://doi.org/10.1038/s41598-021-95823-9 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Fumie Ohtani Dai Miyazaki Yumiko Shimizu Tomoko Haruki Satoru Yamagami Yoshitsugu Inoue |
spellingShingle |
Fumie Ohtani Dai Miyazaki Yumiko Shimizu Tomoko Haruki Satoru Yamagami Yoshitsugu Inoue Role of interferon regulatory factor 7 in corneal endothelial cells after HSV-1 infection Scientific Reports |
author_facet |
Fumie Ohtani Dai Miyazaki Yumiko Shimizu Tomoko Haruki Satoru Yamagami Yoshitsugu Inoue |
author_sort |
Fumie Ohtani |
title |
Role of interferon regulatory factor 7 in corneal endothelial cells after HSV-1 infection |
title_short |
Role of interferon regulatory factor 7 in corneal endothelial cells after HSV-1 infection |
title_full |
Role of interferon regulatory factor 7 in corneal endothelial cells after HSV-1 infection |
title_fullStr |
Role of interferon regulatory factor 7 in corneal endothelial cells after HSV-1 infection |
title_full_unstemmed |
Role of interferon regulatory factor 7 in corneal endothelial cells after HSV-1 infection |
title_sort |
role of interferon regulatory factor 7 in corneal endothelial cells after hsv-1 infection |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2021-08-01 |
description |
Abstract Viral infections of the cornea including herpes simplex virus 1 (HSV-1) cause visual morbidity, and the corneal endothelial cell damage leads to significant visual impairment. Interferon regulatory factor 7 (IRF7) has been identified as a significant regulator in corneal endothelial cells after an HSV-1 infection. To examine the role played by IRF7, the DNA binding domain (DBD) of IRF7 of human corneal endothelial cells (HCEn) was disrupted. An RNAi inhibition of IRF7 and IRF7 DBD disruption (IRF7 ∆DBD) led to an impairment of IFN-β production. Impaired IFN-β production by IRF7 ∆DBD was regained by IRF7 DNA transfection. Transcriptional network analysis indicated that IRF7 plays a role in antigen presentation function of corneal endothelial cells. When the antigen presentation activity of HCEn cells were examined for priming of memory CD8 T cells, IRF7 disruption abolished the anti-viral cytotoxic T lymphocyte (CTL) response which was dependent on the major histocompatibility complex (MHC) class I. To further examine the roles played by IRF7 in CTL induction as acquired immunity, the contribution of IRF7 to MHC class I-mediated antigen presentation was assessed. Analysis of IRF7 ∆DBD cells indicated that IRF7 played an unrecognized role in MHC class I induction, and the viral infection induced-MHC class I induction was abolished by IRF7 disruption. Collectively, the IRF7 in corneal endothelial cells not only contributed to type I IFN response, but also to the mediation of viral infection-induced MHC class I upregulation and priming of CD8 arm of acquired immunity. |
url |
https://doi.org/10.1038/s41598-021-95823-9 |
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