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

Immunology. 2010 Feb;129(2):207-19. doi: 10.1111/j.1365-2567.2009.03165.x. Epub 2009 Jul 18.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cervix Uteri / immunology
  • Cervix Uteri / pathology
  • Elafin / biosynthesis*
  • Elafin / genetics
  • Elafin / immunology*
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism*
  • Epithelial Cells / pathology
  • Fallopian Tubes / pathology
  • Female
  • Follicular Phase / immunology
  • Follicular Phase / metabolism
  • HIV Infections / genetics
  • HIV Infections / immunology*
  • HIV Infections / pathology
  • HIV Infections / physiopathology
  • HIV-1 / immunology*
  • HIV-1 / pathogenicity
  • HeLa Cells
  • Humans
  • Luteal Phase / immunology
  • Luteal Phase / metabolism
  • Poly I-C / immunology
  • Reproduction
  • Uterus / immunology
  • Uterus / pathology*
  • Virulence


  • Elafin
  • Poly I-C