Human Beta Defensin 2 Selectively Inhibits HIV-1 in Highly Permissive CCR6(+)CD4(+) T Cells

Chemokine receptor type 6 (CCR6)(+)CD4(+) T cells are preferentially infected and depleted during HIV disease progression, but are preserved in non-progressors. CCR6 is expressed on a heterogeneous population of memory CD4(+) T cells that are critical to mucosal immunity. Preferential infection of these cells is associated, in part, with high surface expression of CCR5, CXCR4, and α4β7. In addition, CCR6(+)CD4(+) T cells harbor elevated levels of integrated viral DNA and high levels of proliferation markers. We have previously shown that the CCR6 ligands MIP-3α and human beta defensins inhibit HIV replication. The inhibition required CCR6 and the induction of APOBEC3G. Here, we further characterize the induction of apolipoprotein B mRNA editing enzyme (APOBEC3G) by human beta defensin 2. Human beta defensin 2 rapidly induces transcriptional induction of APOBEC3G that involves extracellular signal-regulated kinases 1/2 (ERK1/2) activation and the transcription factors NFATc2, NFATc1, and IRF4. We demonstrate that human beta defensin 2 selectively protects primary CCR6(+)CD4(+) T cells infected with HIV-1. The selective protection of CCR6(+)CD4(+) T cell subsets may be critical in maintaining mucosal immune function and preventing disease progression.