CCR6 ligands inhibit HIV by inducingAPOBEC3G
CCR6 ligands inhibit HIV by inducingAPOBEC3G
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DOI：
10.1182/blood-2009-06-226423
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发表时间：
2010-02-25
期刊：
影响因子：
20.3
通讯作者：
Garzino-Demo, Alfredo
中科院分区：
文献类型：
--
作者：
Lafferty, Mark K.;Sun, Lingling;Garzino-Demo, Alfredo
我们已经确定了一个试验后CCR 6依赖的机制，抑制HIV感染的早期阶段发生的诱导宿主限制性因子载脂蛋白B mRNA编辑酶催化多肽样3G（APOBEC 3G）介导的。我们观察到APOBEC 3G的表达仅在CCR 6（+）细胞中诱导，而在用G抑制（Gi）途径抑制剂百日咳毒素处理的细胞中没有。CCR 6在外周血CD 4（+）CCR 5（+）记忆T细胞上高度表达，并由肠道内的2个CD 4（+）T细胞群α 4 β 7（+）和T辅助细胞17型高度表达，这两种细胞群分别与HIV的细胞间传播和肠道相关淋巴组织内CD 4（+）T细胞的增强恢复有关。这种新的CCR 6介导的抑制机制允许识别诱导对HIV的内在免疫的途径，这可能有助于设计选择性靶向CCR 6（+）细胞的新疗法。（血。2010; 115：1564-1571）
We have identified a postentry CCR6-dependent mechanism of inhibition of HIV occurring at an early stage of infection mediated by the induction of the host restriction factor apolipoprotein B mRNA-editing 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, alpha 4 beta 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)