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Herpes Simplex Virus Type 2 Immediate Early Protein ICP27 Inhibits IFN-β Production in Mucosal Epithelial Cells by Antagonizing IRF3 Activation.

Guan, X; Zhang, M; Fu, M; Luo, S; Hu, Q (2019) Herpes Simplex Virus Type 2 Immediate Early Protein ICP27 Inhibits IFN-β Production in Mucosal Epithelial Cells by Antagonizing IRF3 Activation. Front Immunol, 10. p. 290. ISSN 1664-3224 https://doi.org/10.3389/fimmu.2019.00290
SGUL Authors: Hu, Qinxue

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Abstract

Herpes simplex virus type 2 (HSV-2) is the main cause of genital herpes and infections are common in the lower genital tract. Although neuronal and immune cells can be infected, epithelial cells, and keratinocytes are the primary HSV-2 target cells. HSV-2 establishes latency by evading the host immune system and its infection can also increase the risk of HIV-1 sexual transmission. Our pervious study found that HSV-2 immediate early protein ICP22, inhibited IFN-β production by interfering with the IRF3 pathway. However, ICP22-null HSV-2 did not completely lose the capability of suppressing IFN-β induction, suggesting the involvement of other viral components in the process. In this study, by using an ex vivo cervical explant model, we first demonstrated that HSV-2 can indeed inhibit IFN-β induction in human mucosal tissues. We further identified HSV-2 immediate early protein ICP27 as a potent IFN-β antagonist. ICP27 significantly suppresses the Sendai virus or polyinosinic-polycytidylic acid-induced IFN-β production in human mucosal epithelial cells, showing that ICP27 inhibits the IFN-β promoter activation, and IFN-β production at both mRNA and protein levels. Additional studies revealed that ICP27 directly associates with IRF3 and inhibits its phosphorylation and nuclear translocation, resulting in the inhibition of IFN-β induction. Our findings provide insights into the molecular mechanism underlying HSV-2 mucosal immune evasion, and information for the design of HSV-2 mucosal vaccines.

Item Type: Article
Additional Information: Copyright © 2019 Guan, Zhang, Fu, Luo and Hu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Keywords: HSV-2, ICP27, IFN-β, IRF3, epithelial cells, HSV-2, ICP27, epithelial cells, IFN-beta, IRF3
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: Front Immunol
ISSN: 1664-3224
Language: eng
Dates:
DateEvent
26 February 2019Published
4 February 2019Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
81772192National Natural Science Foundation of Chinahttp://dx.doi.org/10.13039/501100001809
81572009National Natural Science Foundation of Chinahttp://dx.doi.org/10.13039/501100001809
PubMed ID: 30863402
Web of Science ID: WOS:000459675000001
Go to PubMed abstract
URI: http://sgultest.da.ulcc.ac.uk/id/eprint/110749
Publisher's version: https://doi.org/10.3389/fimmu.2019.00290

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