title: TLR4-MyD88/Mal-NF-kB axis is involved in infection of HSV-2 in human cervical epithelial cells.
abstract: We have established an in vitro HSV-2 acute infection model with Human cervical epithelial (HCE cells, the primary target and natural host cells for HSV-2) to investigate the role of TLRs-mediated innate immune response to HSV-2. In current study, we found that HSV-2 infection induced activity of NF-kB reporter and expression of cytokines are TLR4-dependent using approaches with shRNA and TLR4 antagonist. Knockdown experiments demonstrated that the adaptor molecules MyD88 and Mal of the TLRs signaling pathway are required in the HSV-2 induced TLR4-dependent NF-kB activation in HCE cells. Western blot assay suggested that knockdown of TLR4 decreased the phosphorylation of IRAK1 and inhibitor of NF-kB (IkB-α) upon HSV-2 infection. Finally, decreased expression of either TLR4 or MyD88/Mal alone or both significantly abolished productions of IL-6 and IFN-β by ELISA analysis. Taken together, our results from the in vitro infection model reveal for the first time that there exists the pathway via TLR4-Mal/MyD88-IRAK1-NF-kB axis in human cervical epithelial cells in response to HSV-2 infection.
authors.affiliation: 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, Guandong, China.
authors.forename: Hongya
authors.initials: H
authors.lastname: Liu
authors.forename: Kai
authors.initials: K
authors.lastname: Chen
authors.forename: Wenqiang
authors.initials: W
authors.lastname: Feng
authors.forename: Xinxing
authors.initials: X
authors.lastname: Wu
authors.forename: Hui
authors.initials: H
authors.lastname: Li
mesh_terms: D002584:Cervix Uteri / Q000166:cytology / Q000821:virology*; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000821:virology; D005260:Female; D018258:Herpesvirus 2, Human / Q000472:pathogenicity*; D006801:Humans; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins / Q000378:metabolism*; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D016207:Cytokines; C569026:MAL protein, human; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4