Given the presence of Trappin-2/Elafin in the reproductive tract, we tested the ability of recombinant Trappin-2/Elafin to inhibit HIV-1, an important sexually transmitted pathogen. We found that recombinant Trappin-2/Elafin was able to inhibit both T-cell-tropic X4/IIIB and macrophage-tropic R5/BaL HIV-1 in a dose-dependent manner. The inhibitory activity was observed when virus MAPK Inhibitor Library cell line was incubated with Trappin-2/Elafin but

not when Trappin-2/Elafin was added to cells either before infection or after infection. This suggests that the mechanism of inhibition is likely to be a direct interaction between HIV-1 and Trappin-2/Elafin. Additionally, we measured the levels of secreted Trappin-2/Elafin in cervico-vaginal lavages (CVL) from both HIV-positive and HIV-negative women and found that average levels of secreted Trappin-2/Elafin were higher in the CVL from HIV-negative women, although the values did not reach statistical significance. We also found that women at the secretory phase of the menstrual cycle produced more Trappin-2/Elafin in CVL relative to women at the proliferative phase of the menstrual cycle. Our data suggest that Trappin-2/Elafin might be an important endogenous

microbicide of the female reproductive tract that is protective against HIV-1. As the human immunodeficiency virus (HIV)/acquired Sirolimus cost immune-deficiency syndrome (AIDS) pandemic continues, and with the recent failures in vaccine and microbicide trials,1–5 the need for innovative solutions has become essential. Currently, heterosexual transmission accounts for more than 80% of new infections.6,7 Although several studies have found that women are more likely than men to be infected with HIV during vaginal intercourse,8 the transmission rate of HIV from a man to a woman per act of sexual intercourse is still relatively low, ranging from 1:122 to 1:1000.9,10 One reason for this might be that cells of the female reproductive tract (FRT) produce

and secrete a number of endogenous antimicrobials that are protective against HIV.11–15 The mucosal innate immune system of the FRT has to perform the complex immune function of accepting allogeneic Cepharanthine sperm and a semi-allogeneic fetus while preventing pathogen infection. Epithelial cells that line the FRT are the first line of host defense. In addition to presenting a physical barrier, these cells perform a multitude of immune functions. FRT epithelial cells from both the upper and the lower tract express innate immune sensors, such as toll-like receptors (TLR),11,12,16,17 and secretions from these cells have been demonstrated to be antimicrobial.13,18,19 Evidence of innate immune protection has also been described in vivo.