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


METHODS
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.


CONCLUSIONS
This study demonstrates that CCL20/MIP3alpha is an important endogenous anti-HIV-1 microbicide of the female reproductive tract.
Ghosh
Mimi
M
Department of Physiology, Dartmouth Medical School, Lebanon, NH, USA.
Shen
Zheng
Z
Schaefer
Todd M
TM
Fahey
John V
JV
Gupta
Phalguni
P
Wira
Charles R
CR
D019380:Anti-HIV Agents / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D054418:Chemokine CCL20 / Q000276:immunology* / Q000494:pharmacology*; D003713:Dendritic Cells / Q000276:immunology*; D004847:Epithelial Cells / Q000276:immunology / Q000821:virology; D005187:Fallopian Tubes / Q000276:immunology; D005260:Female; D005836:Genitalia, Female / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D011070:Poly I-C / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014599:Uterus / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D000998:Antiviral Agents; C108355:CCL20 protein, human; D054418:Chemokine CCL20; D012333:RNA, Messenger; D011994:Recombinant Proteins; D011070:Poly I-C