Innate immune activation by cGMP-AMP nanoparticles leads to potent and long-acting antiretroviral response against HIV-1

Chukwuemika Aroh, Zhaohui Wang, Nicole Dobbs, Min Luo, Zhijian Chen, Jinming Gao, Nan Yan

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

HIV-1 evades immune detection by the cGAS-STING cytosolic DNA-sensing pathway during acute infection. STING is a critical mediator of type I IFN production, and STING agonists such as cGMP-AMP (cGAMP) and other cyclic dinucleotides elicit potent immune and antitumor response. In this article, we show that administration of cGAMP, delivered by an ultra–pH-sensitive nanoparticle (NP; PC7A), in human 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. cGAMP-PC7A NP-induced protection is mediated through type I IFN signaling and requires monocytes in PBMCs. cGAMP-PC7A NPs also inhibit HIV-1 replication in HIV+ patient PBMCs after ex vivo reactivation. Because pattern recognition receptor agonists continue to show more clinical benefits than the traditional IFN 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.

Original languageEnglish (US)
Pages (from-to)3840-3848
Number of pages9
JournalJournal of Immunology
Volume199
Issue number11
DOIs
StatePublished - Dec 1 2017

ASJC Scopus subject areas

  • Immunology

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