Trappin‐2/Elafin: a novel innate anti‐human immunodeficiency virus‐1 molecule of the human female reproductive tract

Trappin‐2/Elafin is a serine protease inhibitor that plays a major role as an anti‐inflammatory mediator at mucosal surfaces. In addition, Trappin‐2/Elafin has antibacterial activity against Gram‐positive and Gram‐negative bacterial and fungal pathogens. In this study we examined the production of Trappin‐2/Elafin by epithelial cells from the human upper and lower female reproductive tract as well as its activity as an anti‐human immunodeficiency virus (HIV)‐1 molecule. We found that primary uterine, Fallopian tube, cervical and ectocervical epithelial cells produce Trappin‐2/Elafin constitutively and that production of Trappin‐2/Elafin is enhanced following stimulation with Poly(I:C), especially by the uterine cells. 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 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.