Innate Immune Activation by cGMP-AMP Nanoparticles Leads to Potent and Long-Acting Antiretroviral Response against HIV-1.
Innate Immune Activation by cGMP-AMP Nanoparticles Leads to Potent and Long-Acting Antiretroviral Response against HIV-1.
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DOI：
10.4049/jimmunol.1700972
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发表时间：
2017-12-01
期刊：
影响因子：
--
通讯作者：
Yan N
中科院分区：
文献类型：
--
作者：
Aroh C;Wang Z;Dobbs N;Luo M;Chen Z;Gao J;Yan N
HIV-1在急性感染期间通过cGAS-STING胞质DNA传感途径逃避免疫检测。STING是I型干扰素产生的关键介质，STING激动剂如环GMP-AMP （cGAMP）和其他环二核苷酸可引起有效的免疫和抗肿瘤反应。在这里，我们证明了通过超ph敏感纳米颗粒（PC7A）在人外周血单核细胞（PBMCs）中施用cGAMP可诱导针对几种实验室适应和临床HIV-1分离株的有效和长效抗逆转录病毒应答。cGAMP-PC7A NP需要胞吞作用来实现细胞内递送和免疫信号激活，cGAMP-PC7A NP诱导的保护通过I型干扰素信号介导，需要PBMCs中的单核细胞。体外再激活后，cGAMP-PC7A NP也抑制HIV-1在hiv阳性患者pbmc中的复制。随着模式识别受体激动剂比传统干扰素治疗继续显示出更多的临床益处，我们的数据为开发cGAMP或其他STING激动剂作为一类新的免疫刺激长效抗逆转录病毒药物提供了重要证据。
HIV-1 evades immune detection by the cGAS-STING cytosolic DNA sensing pathway during acute infection. STING is a critical mediator of type I interferon production, and STING agonists such as cyclic GMP-AMP (cGAMP) and other cyclic dinucleotides elicit potent immune and anti-tumor response. Here, we show that administration of cGAMP, delivered by an ultra-pH sensitive nanoparticle (PC7A), in human peripheral blood mononuclear cells (PBMCs) induces potent and long-acting antiretroviral response against several laboratory-adapted and clinical HIV-1 isolates. cGAMP-PC7A NP requires endocytosis for intracellular delivery and immune signaling activation, and cGAMP-PC7A NP-induced protection is mediated through type I interferon signaling and requires monocytes in PBMCs. cGAMP-PC7A NP also inhibited HIV-1 replication in HIV-positive patient PBMCs after ex vivo reactivation. As pattern recognition receptor agonists continue to show more clinical benefits than the traditional interferon therapy, our data present important evidence for potentially developing cGAMP or other STING agonists as a new class of immune-stimulating long-acting antiretroviral agents.
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影响因子：
8.8
作者：
Corrales L;Glickman LH;McWhirter SM;Kanne DB;Sivick KE;Katibah GE;Woo SR;Lemmens E;Banda T;Leong JJ;Metchette K;Dubensky TW Jr;Gajewski TF
通讯作者：
Gajewski TF
影响因子：
38.3
作者：
Luo M;Wang H;Wang Z;Cai H;Lu Z;Li Y;Du M;Huang G;Wang C;Chen X;Porembka MR;Lea J;Frankel AE;Fu YX;Chen ZJ;Gao J
通讯作者：
Gao J
影响因子：
15
作者：
Zhou, Kejin;Liu, Haoming;Zhang, Shanrong;Huang, Xiaonan;Wang, Yiguang;Huang, Gang;Sumer, Baran D.;Gao, Jinming
通讯作者：
Gao, Jinming
DOI：
10.1126/science.1244040
发表时间：
2013-09-20
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Li XD;Wu J;Gao D;Wang H;Sun L;Chen ZJ
通讯作者：
Chen ZJ
在pH触发的超分子自组装中合作的分子基础。
影响因子：
16.6
作者：
Li Y;Zhao T;Wang C;Lin Z;Huang G;Sumer BD;Gao J
通讯作者：
Gao J