CCL20/MIP3alpha is a novel anti-HIV-1 molecule of the human female reproductive tract

Am J Reprod Immunol. 2009 Jul;62(1):60-71. doi: 10.1111/j.1600-0897.2009.00713.x.


Problem: CCL20/MIP3alpha is a chemokine for immature dendritic cells as well as an antibacterial against gram-positive and gram-negative bacteria. The role of CCL20/MIP3alpha as an antiviral is unknown. In this study, we have examined the production of CCL20/MIP3alpha by epithelial cells from the upper female reproductive tract as well as its activity as an antiviral molecule.

Method of study: Primary uterine and Fallopian tube epithelial cells were treated with Poly(I:C) and CCL20/MIP3alpha mRNA and protein was measured by Realtime RT-PCR and ELISA assays. Anti-HIV activity was determined using an indicator cell line TZM-bl and quantified by using a luminometer.

Results: Primary uterine and Fallopian tube epithelial cells produce CCL20/MIP3alpha constitutively and the production is enhanced following stimulation with viral double-stranded RNA mimic Poly(I:C). Recombinant CCL20/MIP3alpha was able to inhibit both T-cell-tropic X4/IIIB and macrophage-tropic R5/BaL HIV-1 when virus was directly incubated with CCL20/MIP3alpha but not when CCL20/MIP3alpha was added to cells either prior to infection or post-infection. This suggests that the mechanism of inhibition is likely to be a direct interaction between HIV-1 and CCL20/MIP3alpha.

Conclusion: This study demonstrates that CCL20/MIP3alpha is an important endogenous anti-HIV-1 microbicide of the female reproductive tract.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anti-HIV Agents / pharmacology*
  • Antiviral Agents / pharmacology*
  • Cell Line, Tumor
  • Cells, Cultured
  • Chemokine CCL20 / immunology*
  • Chemokine CCL20 / pharmacology*
  • Dendritic Cells / immunology*
  • Epithelial Cells / immunology
  • Epithelial Cells / virology
  • Fallopian Tubes / immunology
  • Female
  • Genitalia, Female / immunology*
  • Genitalia, Female / virology
  • HIV-1 / drug effects*
  • Humans
  • Poly I-C / pharmacology
  • RNA, Messenger / metabolism
  • Recombinant Proteins / pharmacology
  • Uterus / metabolism
  • Virus Replication / drug effects


  • Anti-HIV Agents
  • Antiviral Agents
  • CCL20 protein, human
  • Chemokine CCL20
  • RNA, Messenger
  • Recombinant Proteins
  • Poly I-C