IMMUNOBIOLOGY CCR6 ligands inhibit HIV by inducing APOBEC3G

We have identified a postentry CCR6dependent mechanism of inhibition of HIV occurring at an early stage of infection mediated by the induction of the host restriction factor apolipoprotein B mRNAediting enzyme-catalytic polypeptide-like 3G (APOBEC3G). We observed induction of APOBEC3G expression only in CCR6 cells but not in cells treated with the G inhibitory (Gi) pathway inhibitor pertussis toxin. CCR6 is highly expressed on peripheral blood CD4 CCR5 memory T cells and by 2 populations of CD4 T cells within the gut, 4 7 and T helper type 17, that have been implicated in cell-to-cell spread of HIV and enhanced restoration of CD4 T cells within gut-associated lymphoid tissue, respectively. This novel CCR6-mediated mechanism of inhibition allows the identification of pathways that induce intrinsic immunity to HIV, which could be useful in devising novel therapeutics that selectively target CCR6 cells. (Blood. 2010;115:1564-1571)