ORIGINAL ARTICLE: CCL20/MIP3α is a Novel Anti-HIV-1 Molecule of the Human Female Reproductive Tract


Dr M. Ghosh, Department of Physiology, Dartmouth Medical School, 710W Borwell, 1 Medical Center Drive, Lebanon, NH 03756, USA.
E-mail: mimi.ghosh@dartmouth.edu


Problem  CCL20/MIP3α is a chemokine for immature dendritic cells as well as an antibacterial against gram-positive and gram-negative bacteria. The role of CCL20/MIP3α as an antiviral is unknown. In this study, we have examined the production of CCL20/MIP3α 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/MIP3α 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/MIP3α constitutively and the production is enhanced following stimulation with viral double-stranded RNA mimic Poly(I:C). Recombinant CCL20/MIP3α was able to inhibit both T-cell-tropic X4/IIIB and macrophage-tropic R5/BaL HIV-1 when virus was directly incubated with CCL20/MIP3α but not when CCL20/MIP3α 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/MIP3α.

Conclusion  This study demonstrates that CCL20/MIP3α is an important endogenous anti-HIV-1 microbicide of the female reproductive tract.