{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:02:04Z","timestamp":1790787724062,"version":"4.1.0"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2017,12,1]],"date-time":"2017-12-01T00:00:00Z","timestamp":1512086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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\u2013pH-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.<\/jats:p>","DOI":"10.4049\/jimmunol.1700972","type":"journal-article","created":{"date-parts":[[2017,10,30]],"date-time":"2017-10-30T09:15:09Z","timestamp":1509354909000},"page":"3840-3848","source":"Crossref","is-referenced-by-count":46,"title":["Innate Immune Activation by cGMP-AMP Nanoparticles Leads to Potent and Long-Acting Antiretroviral Response against HIV-1"],"prefix":"10.1093","volume":"199","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4972-5232","authenticated-orcid":false,"given":"Chukwuemika","family":"Aroh","sequence":"first","affiliation":[{"name":"Department of Immunology, University of Texas Southwestern Medical Center , Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaohui","family":"Wang","sequence":"additional","affiliation":[{"name":"Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center , Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1944-9740","authenticated-orcid":false,"given":"Nicole","family":"Dobbs","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Texas Southwestern Medical Center , Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Luo","sequence":"additional","affiliation":[{"name":"Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center , Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijian","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, University of Texas Southwestern Medical Center , Dallas, TX 75390"},{"name":"Howard Hughes Medical Institute, University of Texas Southwestern Medical Center , Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinming","family":"Gao","sequence":"additional","affiliation":[{"name":"Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center , Dallas, TX 75390"},{"name":"Department of Pharmacology, University of Texas Southwestern Medical Center , Dallas, TX 75390"},{"name":"Department of Otolaryngology, University of Texas Southwestern Medical Center , Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Texas Southwestern Medical Center , Dallas, TX 75390"},{"name":"Department of Microbiology, University of Texas Southwestern Medical Center , Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,12,1]]},"reference":[{"key":"2025030615034103300_r1","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1038\/ni.2229","article-title":"Intrinsic antiviral immunity","volume":"13","author":"Yan","year":"2012","journal-title":"Nat. Immunol."},{"key":"2025030615034103300_r2","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1038\/ni.1941","article-title":"The cytosolic exonuclease TREX1 inhibits the innate immune response to human immunodeficiency virus type 1","volume":"11","author":"Yan","year":"2010","journal-title":"Nat. Immunol."},{"key":"2025030615034103300_r3","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1126\/science.1240933","article-title":"Cyclic GMP-AMP synthase is an innate immune sensor of HIV and other retroviruses","volume":"341","author":"Gao","year":"2013","journal-title":"Science"},{"key":"2025030615034103300_r4","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1016\/j.celrep.2016.04.048","article-title":"TREX1 knockdown induces an interferon response to HIV that delays viral infection in humanized mice","volume":"15","author":"Wheeler","year":"2016","journal-title":"Cell Rep."},{"key":"2025030615034103300_r5","doi-asserted-by":"crossref","first-page":"193","DOI":"10.3389\/fmicb.2014.00193","article-title":"Safeguard against DNA sensing: the role of TREX1 in HIV-1 infection and autoimmune diseases","volume":"5","author":"Hasan","year":"2014","journal-title":"Front. Microbiol."},{"key":"2025030615034103300_r6","doi-asserted-by":"crossref","first-page":"S297","DOI":"10.1086\/655657","article-title":"Innate immune activation in primary HIV-1 infection","volume":"202","author":"Chang","year":"2010","journal-title":"J. Infect. Dis."},{"key":"2025030615034103300_r7","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1126\/science.1244040","article-title":"Pivotal roles of cGAS-cGAMP signaling in antiviral defense and immune adjuvant effects","volume":"341","author":"Li","year":"2013","journal-title":"Science"},{"key":"2025030615034103300_r8","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/nrc.2016.14","article-title":"Antitumour actions of interferons: implications for cancer therapy","volume":"16","author":"Parker","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"2025030615034103300_r9","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1073\/pnas.1621363114","article-title":"cGAS is essential for the antitumor effect of immune checkpoint blockade","volume":"114","author":"Wang","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030615034103300_r10","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1016\/j.celrep.2015.04.031","article-title":"Direct activation of STING in the tumor microenvironment leads to potent and systemic tumor regression and immunity","volume":"11","author":"Corrales","year":"2015","journal-title":"Cell Reports"},{"key":"2025030615034103300_r11","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1038\/nchembio.1661","article-title":"Hydrolysis of 2\u20323\u2032-cGAMP by ENPP1 and design of nonhydrolyzable analogs","volume":"10","author":"Li","year":"2014","journal-title":"Nat. Chem. Biol."},{"key":"2025030615034103300_r12","doi-asserted-by":"crossref","first-page":"13214","DOI":"10.1038\/ncomms13214","article-title":"Molecular basis of cooperativity in pH-triggered supramolecular self-assembly","volume":"7","author":"Li","year":"2016","journal-title":"Nat. Commun."},{"key":"2025030615034103300_r13","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1038\/nnano.2017.52","article-title":"A STING-activating nanovaccine for cancer immunotherapy","volume":"12","author":"Luo","year":"2017","journal-title":"Nat. Nanotechnol."},{"key":"2025030615034103300_r14","doi-asserted-by":"crossref","first-page":"e50859","DOI":"10.1371\/journal.pone.0050859","article-title":"Quantification of reverse transcriptase activity by real-time PCR as a fast and accurate method for titration of HIV, lenti- and retroviral vectors","volume":"7","author":"Vermeire","year":"2012","journal-title":"PLoS One"},{"key":"2025030615034103300_r15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jviromet.2008.10.012","article-title":"A one-step SYBR Green I-based product-enhanced reverse transcriptase assay for the quantitation of retroviruses in cell culture supernatants","volume":"156","author":"Pizzato","year":"2009","journal-title":"J. Virol. Methods"},{"key":"2025030615034103300_r16","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1002\/anie.201610302","article-title":"A redox-activatable fluorescent sensor for the high-throughput quantification of cytosolic delivery of macromolecules","volume":"56","author":"Wang","year":"2017","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"2025030615034103300_r17","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.chom.2015.07.001","article-title":"STING activation by translocation from the ER is associated with infection and autoinflammatory disease","volume":"18","author":"Dobbs","year":"2015","journal-title":"Cell Host Microbe"},{"key":"2025030615034103300_r18","doi-asserted-by":"crossref","first-page":"7803","DOI":"10.1021\/ja300176w","article-title":"Multicolored pH-tunable and activatable fluorescence nanoplatform responsive to physiologic pH stimuli","volume":"134","author":"Zhou","year":"2012","journal-title":"J. Am. Chem. Soc."},{"key":"2025030615034103300_r19","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.molcel.2013.05.022","article-title":"Cyclic GMP-AMP containing mixed phosphodiester linkages is an endogenous high-affinity ligand for STING","volume":"51","author":"Zhang","year":"2013","journal-title":"Mol. Cell"},{"key":"2025030615034103300_r20","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1097\/COH.0000000000000219","article-title":"The promise and pitfalls of long-acting injectable agents for HIV prevention","volume":"11","author":"Landovitz","year":"2016","journal-title":"Curr. Opin. HIV AIDS"},{"key":"2025030615034103300_r21","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1146\/annurev-immunol-032414-112043","article-title":"Innate immune recognition of cancer","volume":"33","author":"Woo","year":"2015","journal-title":"Annu. Rev. Immunol."},{"key":"2025030615034103300_r22","doi-asserted-by":"crossref","first-page":"283ra52","DOI":"10.1126\/scitranslmed.aaa4306","article-title":"STING agonist formulated cancer vaccines can cure established tumors resistant to PD-1 blockade","volume":"7","author":"Fu","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"2025030615034103300_r23","first-page":"59","article-title":"CROI 2016: advances in antiretroviral therapy","volume":"24","author":"Taylor","year":"2016","journal-title":"Top. Antivir. Med."},{"key":"2025030615034103300_r24","doi-asserted-by":"crossref","first-page":"e02166","DOI":"10.1128\/JVI.02166-16","article-title":"Toll-like receptor 7 agonist GS-9620 induces HIV expression and HIV-specific immunity in cells from HIV-infected individuals on suppressive antiretroviral therapy","volume":"91","author":"Tsai","year":"2017","journal-title":"J. Virol."},{"key":"2025030615034103300_r25","doi-asserted-by":"crossref","first-page":"4441","DOI":"10.1128\/JVI.00222-16","article-title":"A novel Toll-like receptor 9 agonist, MGN1703, enhances HIV-1 transcription and NK cell-mediated inhibition of HIV-1-infected autologous CD4+ T cells","volume":"90","author":"Offersen","year":"2016","journal-title":"J. Virol."},{"key":"2025030615034103300_r26","doi-asserted-by":"crossref","first-page":"A41","DOI":"10.1089\/aid.2014.5066.abstract","article-title":"Inhibiting the host exonuclease TREX1 induces a localized and protective host interferon response against acute HIV infection in vivo","volume":"30","author":"Wheeler","year":"2014","journal-title":"AIDS Res. Hum. Retroviruses"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/199\/11\/3840\/61592684\/ji1700972.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/199\/11\/3840\/61592684\/ji1700972.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T12:14:43Z","timestamp":1741263283000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/199\/11\/3840\/7977082"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12,1]]},"references-count":26,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2017,12,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1700972","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2017,12]]},"published":{"date-parts":[[2017,12,1]]}}}