Recently HSV-2 has been recognized as a potentially important factor in the pathogenesis of Kaposi’s sarcoma. HSV-2 infects the genital epithelium and can be transmi ed to the central nervous system to establish life-long latent infection. Current treatments with anti-viral therapy are commonly used to control re-activation of HSV-2. However, these medications do not eliminate latent virus. The increasing incidence and prevalence of HSV-2 and its association with significant morbidity and mortality has urged us to uncover its fundamental mechanisms. The genital mucosa is the first line of defense against sexually transmi ed Praeruptorin-B pathogens and plays a crucial role in innate immunity and adaptive immunity as well. HSV-2 primarily infects genital epithelium and replicates within the vaginal keratinocytes. Recently, a Canadian group investigated the susceptibility of primary human female genital epithelial cells to HSV-2 using an ex 
vivo culture model. By using TLR ligands, they assessed the anti-viral activity of human female genital epithelium in Ergosterol response to HSV-2 and the role of HSV-2 virion host shutoff protein on innate dsRNA antiviral pathways in human vaginal epithelial cells. But to date, li le is known about the innate immune pathways of human genital epithelial cells in response to HSV-2 infection. Although it has been shown that multiple Toll-like receptors are involved in recognition of different HSV strains and contribute to the immune response to HSV infection. Most of these studies have used immunocompetent cells or mice model. There appears discrepancy while assessing the role of NK cells, conventional dendritic cells and plasmacytoid DCs in HSV-2 infection. One of the assignable facts is that HSV-2 does not directly infect DCs. IFN-b production or IFN-sensing pathways have been shown pronounced differences between human DCs and genital epithelial cells. It has been realized that the experimental immunology studies should link directly to the diseases caused by HSV in humans. Therefore, our recent study has focused on the human primary target cells of HSV-2 and established an in vitro HSV-2 acute infection model with Human Cervical Epithelial cells to investigate the role of TLRs-mediated innate immune response to HSV-2. IFN-beta plays a critical role in antiviral activity during the initial HSV-2 infection of genital epithelium. Different cell types are likely to have their own preferred pathways to induce type I IFN in response to different viruses. The interferonregulatory factor family of transcription factors are differentially activated and function as important mediators of IFNs, for example, IRF8 and IRF3 cooperatively regulate IFN-b induction in human monocytes to respond Sendai Virus. But there is discrepancy if IRF7 is required for the induction of IFN-b upon virus infection. It is worthwhile to investigate the key IRF family members in regulating IFN-b expression downstream of TLRs in response to HSV-2. We have shown that HSV-2 infection up-regulates TLR4 expression and activates NF-kB, and over-expression of TLR4/ MD2 augments viral-induced NF-kB activation. In the current study, we found that HSV-2 infection activates TLR4-dependent IRF3 and IRF7 which are key players in regulating TLR-mediated type I IFN expression.