HSV-2 increases TLR4-dependent phosphorylated IRFs and IFN-β induction in cervical epithelial cells.
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.
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.
Hongya
H
Liu
Central Blood Station of Rizhao, Rizhao, Shandong, China.
Kai
K
Chen
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.
Wenqiang
W
Feng
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.
Juanjuan
J
Guo
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.
Hui
H
Li
D002584:Cervix Uteri / Q000166:cytology / Q000378:metabolism* / Q000821:virology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism* / Q000821:virology; D005260:Female; D018258:Herpesvirus 2, Human; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000378:metabolism*; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*
D050835:Interferon Regulatory Factors; D016328:NF-kappa B; D034741:RNA, Small Interfering; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D016899:Interferon-beta