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HSV-2 Infection of Human Genital Epithelial Cells Upregulates TLR9 Expression Through the SP1/JNK Signaling Pathway

Hu, K; Fu, M; Wang, J; Luo, S; Barreto, M; Singh, R; Chowdhury, T; Li, M; Zhang, M; Guan, X; et al. Hu, K; Fu, M; Wang, J; Luo, S; Barreto, M; Singh, R; Chowdhury, T; Li, M; Zhang, M; Guan, X; Xiao, J; Hu, Q (2020) HSV-2 Infection of Human Genital Epithelial Cells Upregulates TLR9 Expression Through the SP1/JNK Signaling Pathway. Frontiers in Immunology, 11. p. 356. ISSN 1664-3224 https://doi.org/10.3389/fimmu.2020.00356
SGUL Authors: Hu, Qinxue

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Abstract

It is known that herpes simplex virus type 2 (HSV-2) triggers the activation of Toll-like receptor (TLR) 9 signaling pathway and the consequent production of antiviral cytokines in dendritic cells. However, the impact of HSV-2 infection on TLR9 expression and signaling in genital epithelial cells, the primary HSV-2 targets, has yet to be determined. In the current study, by using both human genital epithelial cell lines and primary genital epithelial cells as models, we found that HSV-2 infection enhances TLR9 expression at both mRNA and protein levels. Such enhancement is virus replication-dependent and CpG-independent, while the HSV-2-mediated upregulation of TLR9 does not activate TLR9 signaling pathway. Mechanistically, a SP1 binding site on TLR9 promoter appears to be essential for HSV-2-induced TLR9 transactivation. Upon HSV-2 infection, SP1 translocates from the cytoplasm to the nucleus, and consequently binds to TLR9 promoter. By using specific inhibitors, the JNK signaling pathway is shown to be involved in the HSV-2-induced TLR9 transactivation, while HSV-2 infection increases the phosphorylation but not the total level of JNK. In agreement, antagonism of JNK signaling pathway inhibits the HSV-2-induced SP1 nuclear translocation. Taken together, our study demonstrates that HSV-2 infection of human genital epithelial cells promotes TLR9 expression through SP1/JNK signaling pathway. Findings in this study provide insights into HSV-2-host interactions and potential targets for immune intervention.

Item Type: Article
Additional Information: Copyright © 2020 Hu, Fu, Wang, Luo, Barreto, Singh, Chowdhury, Li, Zhang, Guan, Xiao 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.
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: Frontiers in Immunology
ISSN: 1664-3224
Dates:
DateEvent
4 March 2020Published
13 February 2020Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
201604910184China Scholarship Councilhttp://dx.doi.org/10.13039/501100004543
201603780050China Scholarship Councilhttp://dx.doi.org/10.13039/501100004543
201603780050British Councilhttp://dx.doi.org/10.13039/501100000308
81772192National Natural Science Foundation of Chinahttp://dx.doi.org/10.13039/501100001809
31500146National Natural Science Foundation of Chinahttp://dx.doi.org/10.13039/501100001809
81860310National Natural Science Foundation of Chinahttp://dx.doi.org/10.13039/501100001809
URI: http://openaccess.sgul.ac.uk/id/eprint/111716
Publisher's version: https://doi.org/10.3389/fimmu.2020.00356

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