HSV-2 increases TLR4-dependent phosphorylated IRFs and IFN-β induction in cervical epithelial cells

Hongya Liu; Kai Chen; Wenqiang Feng; Juanjuan Guo; Hui Li

doi:10.1371/journal.pone.0094806

HSV-2 increases TLR4-dependent phosphorylated IRFs and IFN-β induction in cervical epithelial cells

PLoS One. 2014 Apr 10;9(4):e94806. doi: 10.1371/journal.pone.0094806. eCollection 2014.

Authors

Hongya Liu¹, Kai Chen², Wenqiang Feng¹, Juanjuan Guo¹, Hui Li¹

Affiliations

¹ State Key Laboratory of Virology, Institute of Medical Virology, Wuhan University School of Medicine, Wuhan, Hubei, China; Shengzhen R&D Center of State Key Laboratory of Virology, Wuhan University Shenzhen Institute, Shenzhen, Guangdong, China.
² Central Blood Station of Rizhao, Rizhao, Shandong, China.

Abstract

Our previous studies demonstrated that HSV-2 infection up-regulates TLR4 expression and induces NF-kB activity, thereby facilitating innate immune response in human cervical epithelial cells. This process requires involvement of TLR4 adaptors, Mal and MyD88. In the current study, we found that HSV-2 infection increases levels of phosphoryalted IRF3 and IRF7, then regulating expression of type I IFN. As expected, these changes induced by HSV-2 infection depended upon TLR4. Knockdown of TRIF and/or TRAM by siRNAs indicated that TRIF/TRAM might be involved in expression of IFN-β. Our results demonstrate for the first time that IRF3 and IRF7 are both involved in inducing TLR4-dependent IFN-β expression in response to HSV-2 in its primary infected genital epithelial cells. Thus, TLR4-Mal/MyD88 and TLR4-TRIF/TRAM signaling may synergize and/or cooperate in innate immune response of cervical epithelial cells to HSV-2 infection.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cervix Uteri / cytology
Cervix Uteri / metabolism*
Cervix Uteri / virology
Epithelial Cells / cytology
Epithelial Cells / metabolism*
Epithelial Cells / virology
Female
Herpesvirus 2, Human*
Humans
Interferon Regulatory Factors / genetics
Interferon Regulatory Factors / metabolism*
Interferon-beta / genetics
Interferon-beta / metabolism*
NF-kappa B / metabolism
Phosphorylation
RNA, Small Interfering
Signal Transduction / physiology
Toll-Like Receptor 4 / genetics
Toll-Like Receptor 4 / metabolism*

Substances

Interferon Regulatory Factors
NF-kappa B
RNA, Small Interfering
TLR4 protein, human
Toll-Like Receptor 4
Interferon-beta

Grants and funding

This work was supported by National Natural Science Foundation of China (81072419). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.