Human Beta Defensin 2 Selectively Inhibits HIV-1 in Highly Permissive CCR6⁺CD4⁺ T Cells.
Human Beta Defensin 2 Selectively Inhibits HIV-1 in Highly Permissive CCR6⁺CD4⁺ T Cells.
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DOI：
10.3390/v9050111
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发表时间：
2017-05-16
期刊：
影响因子：
--
通讯作者：
Garzino-Demo A
中科院分区：
文献类型：
--
作者：
Lafferty MK;Sun L;Christensen-Quick A;Lu W;Garzino-Demo A
趋化因子受体6型(CCR6)+CD4+ T细胞在HIV疾病进展过程中优先被感染和耗尽，但在非进展者中保留。CCR6在对粘膜免疫至关重要的记忆性CD4+ T细胞的异质群体中表达。这些细胞的优先感染部分与CCR5、CXCR4和α4β7的高表面表达有关。此外，CCR6+CD4+ T细胞具有高水平的整合病毒DNA和高水平的增殖标志物。我们之前已经证明CCR6配体MIP-3α和人β防御素抑制HIV复制。这种抑制需要CCR6和APOBEC3G的诱导。在这里，我们进一步表征了人β防御素2对载脂蛋白B mRNA编辑酶（APOBEC3G）的诱导作用。人β -防御素2快速诱导APOBEC3G的转录诱导，涉及细胞外信号调节激酶1/2 （ERK1/2）激活和转录因子NFATc2、NFATc1和IRF4。我们证明了人类β -防御蛋白2选择性地保护感染HIV-1的原代CCR6+CD4+ T细胞。CCR6+CD4+ T细胞亚群的选择性保护可能对维持粘膜免疫功能和预防疾病进展至关重要。
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.
影响因子：
3.7
作者：
Guan Y;Abdelwahab S;Kamin-Lewis R;DeVico AL;Lewis GK
通讯作者：
Lewis GK