TLR4 augments HSV-2 induced NF-κB activity in human cervical epithelial cells (136.28)

Herpes simplex virus type 2 (HSV-2) infects the genital epithelium and can be transmitted to the central nervous system, establishing lifelong infection. Toll-like receptors (TLRs) have been reported to initiate innate immune responses to microorganisms. It has been shown that TLR2 and TLR9 are involved in recognition of different HSV strains by dendritic cells (DCs). Our previous study has shown that HSV-2 infection leads to dramatic activation of the NF-κB signaling pathway and induction of IL-6 and IFN-beta. We report here that HSV-2 activates NF-κB reporter and TLR4/MD2 augments this activation. The NF-κB reporter construct was co-transfected into human cervical epithelial (HCE) cells together with either vectors or TLR4/MD2 expression plasmids. The transfected cells were then infected with HSV-2 at 3 MOI and luciferase activity was measured and normalized to Renilla luciferase activity. We observed a relatively low, but reproducible induction (approximately 1.5-fold) of reporter activity in HCE cells with HSV-2 infection compared to that in mock-infected cells. Importantly, an augmented induction of the NF-κB reporter was seen while cells were co-transfected with TLR4/MD2 in HSV-2 infected cells. Thus, TLR4 potentially plays a role in mediating its activation. Effect of shRNA against TLR4 on this induction is under active investigation. This work was supported by grants from the National Natural Science Foundation of China (No. 30500465, 30810103052)