Antiviral Activity of Trappin-2 and Elafin In Vitro and In Vivo against Genital Herpes

摘要: Serine protease inhibitor elafin (E) and its precursor, trappin-2 (Tr), have been associated with mucosal resistance to HIV-1 infection. We recently showed that Tr/E are among principal anti-HIV-1 molecules in cervicovaginal lavage (CVL) fluid, E is ∼130 times more potent than Tr against HIV-1, inhibited attachment transcytosis across human genital epithelial cells (ECs). Since herpes simplex virus 2 (HSV-2) a major sexually transmitted infection risk factor for transmission, we assessed contribution defense HSV-2. Our vitro studies demonstrated pretreatment of endometrial (HEC-1A) endocervical (End1/E6E7) ECs Tr-expressing adenovirus (Ad/Tr) or recombinant proteins before after HSV-2 resulted significantly reduced titers compared those controls. Interestingly, was ∼7 Tr. Conversely, knockdown endogenous by small interfering RNA (siRNA) increased replication ECs. Recombinant viral acting indirectly on cells. Further, lower secretion proinflammatory interleukin 8 (IL-8) tumor necrosis alpha (TNF-α) decreased NF-κB nuclear translocation. Additionally, protected Ad/Tr-treated enhanced interferon regulatory 3 (IRF3) translocation antiviral IFN-β response Lastly, vivo intravaginal Tr-transgenic mice (Etg) despite similar the tract, Etg had load TNF-α central nervous system Collectively, this first experimental evidence highlighting anti-HSV-2 activity female mucosa.