scholarly journals Role of Interferon Regulatory Factor 7 in Corneal Endothelial Cells After HSV-1 Infection

2021 ◽  
Author(s):  
Fumie Ohtani ◽  
Dai Miyazaki ◽  
Yumiko Shimizu ◽  
Tomoko Haruki ◽  
Satoru Yamagami ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Antigen Presentation ◽  
Mhc Class I ◽  
Interferon Regulatory Factor ◽  
Class I ◽  
Acquired Immunity ◽  
Corneal Endothelial Cells ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 7 ◽  
Hsv 1

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 impairment of IFN-β production. Impaired IFN-β production by IRF7 ∆DBD was regained by IRF7 DNA transfection. Transcriptional network analysis indicated that IRF7 played 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 CTL response, which was dependent on major histocompatibility complex (MHC) class I.To further examine roles of IRF7 in CTL induction as acquired immunity, contribution of IRF7 to MHC class I-mediated antigen presentation was assessed. Analysis of IRF7 ∆DBD cells indicated that IRF7 has previously unrecognized role in MHC class I induction, and viral infection induced-MHC class I induction was abolished by IRF7 disruption.Collectively, the IRF7 in corneal endothelial cells not only contributes to type I IFN response, but also mediates viral infection-induced MHC class I upregulation and priming of CD8 arm of acquired immunity.

scholarly journals Role of interferon regulatory factor 7 in corneal endothelial cells after HSV-1 infection

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fumie Ohtani ◽  
Dai Miyazaki ◽  
Yumiko Shimizu ◽  
Tomoko Haruki ◽  
Satoru Yamagami ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Antigen Presentation ◽  
Mhc Class I ◽  
Interferon Regulatory Factor ◽  
Class I ◽  
Acquired Immunity ◽  
Corneal Endothelial Cells ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 7 ◽  
Hsv 1

AbstractViral 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.

scholarly journals A Novel Interferon Regulatory Factor (IRF), IRF-10, Has a Unique Role in Immune Defense and Is Induced by the v-Rel Oncoprotein

2002 ◽  
Vol 22 (11) ◽  
pp. 3942-3957 ◽  
Author(s):  
Jiří Nehyba ◽  
Radmila Hrdličková ◽  
Joan Burnside ◽  
Henry R. Bose
Keyword(s):  
Mhc Class I ◽  
Target Genes ◽  
Interferon Regulatory Factor ◽  
Inducible Expression ◽  
Immune Defense ◽  
Class I ◽  
Type I ◽  
Regulatory Factor ◽  
Unique Role ◽  
Ifn Γ

ABSTRACT The cloning and functional characterization of a novel interferon regulatory factor (IRF), IRF-10, are described. IRF-10 is most closely related to IRF-4 but differs in both its constitutive and inducible expression. The expression of IRF-10 is inducible by interferons (IFNs) and by concanavalin A. In contrast to that of other IRFs, the inducible expression of IRF-10 is characterized by delayed kinetics and requires protein synthesis, suggesting a unique role in the later stages of an antiviral defense. Accordingly, IRF-10 is involved in the upregulation of two primary IFN-γ target genes (major histocompatibility complex [MHC] class I and guanylate-binding protein) and interferes with the induction of the type I IFN target gene for 2′,5′-oligo(A) synthetase. IRF-10 binds the interferon-stimulated response element site of the MHC class I promoter. In contrast to that of IRF-1, which has some of the same functional characteristics, the expression of IRF-10 is not cytotoxic for fibroblasts or B cells. The expression of IRF-10 is induced by the oncogene v-rel, the proto-oncogene c-rel, and IRF-4 in a tissue-specific manner. Moreover, v-Rel and IRF-4 synergistically cooperate in the induction of IRF-10 in fibroblasts. The level of IRF-10 induction in lymphoid cell lines by Rel proteins correlates with Rel transformation potential. These results suggest that IRF-10 plays a role in the late stages of an immune defense by regulating the expression some of the IFN-γ target genes in the absence of a cytotoxic effect. Furthermore, IRF-10 expression is regulated, at least in part, by members of the Rel/NF-κB and IRF families.

scholarly journals Inhibition of Major Histocompatibility Complex Class I Antigen Presentation in Pig and Primate Cells by Herpes Simplex Virus Type 1 and 2 ICP47

1998 ◽  
Vol 72 (6) ◽  
pp. 5076-5084 ◽  
Author(s):  
Pieter Jugovic ◽  
Ann M. Hill ◽  
Roman Tomazin ◽  
Hidde Ploegh ◽  
David C. Johnson
Keyword(s):  
Major Histocompatibility Complex ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Antigen Presentation ◽  
Mhc Class I ◽  
Class I ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) express an immediate-early protein, ICP47, that effectively inhibits the human transporter associated with antigen presentation (TAP), blocking major histocompatibility complex (MHC) class I antigen presentation to CD8+ T cells. Previous work indicated that the mouse TAP is relatively resistant to inhibition by the HSV-1 and HSV-2 ICP47 proteins (ICP47-1 and ICP47-2) and that mouse cells infected with HSV-1 are lysed by anti-HSV CD8+ cytotoxic T lymphocytes (CTL). Therefore, mice are apparently not suitable animals in which to study the in vivo effects of ICP47. In order to find an animal model, we introduced ICP47-1 and ICP47-2 into cells from various animal species—mice, rats, guinea pigs, rabbits, dogs, pigs, cows, monkeys, and humans—and measured TAP activity in the cells. Both proteins were unable to inhibit TAP in mouse, rat, guinea pig, and rabbit cells. In contrast, ICP47-1 and ICP47-2 inhibited TAP in pig, dog, cow, and monkey cells, and the TAP in pig and dog fibroblasts was often more sensitive to both proteins than TAP in human fibroblasts. These results were extended by measuring CD8+-T-cell recognition (CTL lysis) of cells from various species. Cells were infected with recombinant HSV-1 constructed to express murine MHC class I proteins so that the cells would be recognized and lysed by well-characterized murine anti-HSV CTL unless antigen presentation was blocked by ICP47. Anti-HSV CD8+ CTL effectively lysed pig and primate cells infected with a recombinant HSV-1 ICP47− mutant but were unable to lyse pig or primate cells infected with a recombinant HSV-1 that expressed ICP47. Therefore, pigs, dogs, and monkeys may be useful animal models in which to test the effects of ICP47 on HSV pathogenesis or the use of ICP47 as a selective immunosuppressive agent.

Sign in / Sign up

Export Citation Format

Share Document