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PQBP1 是cGAS依赖于HIV-1的先天反应的近端传感器

Sunnie M Yoh¹, Monika Schneider¹, Janna Seifried²

¹Infectious and Inflammatory Disease Center, Sanford-Burnham Medical Research Institute, 10901 N. Torrey Pines Rd., La Jolla, CA 92116.

|June 6, 2015

概括

聚聚氨胺结合蛋白1 (PQBP1) 在树突细胞中充当HIV-1感染的传感器. 它通过与cGAS相互作用触发先天性免疫反应,这对抗病毒防御至关重要.

科学领域:

免疫学免疫学免疫学
病毒学病毒学
细胞生物学细胞生物学

背景情况:

树突细胞 (DCs) 对于抗病毒免疫至关重要,弥合了先天和适应性反应.
人类免疫缺陷病毒1型 (HIV-1) 感染DCs激活了一种依赖IRF3的先天免疫通路,涉及循环GAMP合成酶 (cGAS).

研究的目的:

在人类单细胞衍生的树突细胞 (MDDCs) 中直接感知HIV-1感染的免疫调节剂的识别.
阐明已识别的调节因子在启动对HIV-1的先天免疫反应中的作用.

主要方法:

针对性RNA干扰 (RNAi) 选对初级人类MDDC进行了选.
进行了相互作用测定,以确认PQBP1,HIV-1 DNA和cGAS之间的结合.
在Renpenning综合征患者的MDDC中评估了对HIV-1的先天免疫反应,这些患者具有PQBP1突变.

主要成果:

聚聚胺结合蛋白1 (PQBP1) 被确定为检测HIV-1感染的关键调节器.
PQBP1直接与逆转录的HIV-1DNA结合,并与cGAS相互作用.
来自Renpenning综合征患者的MDDC显示出对HIV-1的先天免疫反应显著降低.

结论:

在树突细胞中,PQBP1作为HIV-1感染的近端先天传感器.
通过与cGAS的相互作用,PQBP1启动了一种依赖IRF3的先天免疫反应.
在人类树突细胞中,PQBP1对于HIV-1的先天免疫感应至关重要.

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