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GS-9620 suppressed hepatitis B virus (HBV) in animal models of chronic infection and transiently activated HIV expression<jats:italic>ex vivo<\/jats:italic>in latently infected peripheral blood mononuclear cells (PBMCs) from virally suppressed patients. Currently, GS-9620 is under clinical evaluation for treating chronic HBV infection and for reducing latent reservoirs in virally suppressed HIV-infected patients. Here, we investigated the<jats:italic>in vitro<\/jats:italic>anti-HIV-1 activity of GS-9620. GS-9620 potently inhibited viral replication in PBMCs, particularly when it was added 24 to 48 h prior to HIV infection (50% effective concentration = 27 nM). Depletion of pDCs but not other immune cell subsets from PBMC cultures suppressed GS-9620 antiviral activity. Although GS-9620 was inactive against HIV in purified CD4<jats:sup>+<\/jats:sup>T cells and macrophages, HIV replication was potently inhibited by conditioned medium derived from GS-9620-treated pDC cultures when added to CD4<jats:sup>+<\/jats:sup>T cells prior to infection. This suggests that GS-9620-mediated stimulation of PBMCs induced the production of a soluble factor(s) inhibiting HIV replication in<jats:italic>trans<\/jats:italic>. GS-9620-treated PBMCs primarily showed increased production of interferon alpha (IFN-\u03b1), and cotreatment with IFN-\u03b1-blocking antibodies reversed the HIV-1-inhibitory effect of GS-9620. Additional studies demonstrated that GS-9620 inhibited a postentry event in HIV replication at a step coincident with or prior to reverse transcription. The simultaneous activation of HIV-1 expression and inhibition of HIV-1 replication are important considerations for the clinical evaluation of GS-9620 since these antiviral effects may help restrict potential local HIV spread upon<jats:italic>in vivo<\/jats:italic>latency reversal.<\/jats:p>","DOI":"10.1128\/aac.01369-16","type":"journal-article","created":{"date-parts":[[2016,11,1]],"date-time":"2016-11-01T01:20:26Z","timestamp":1477963226000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":50,"title":["TLR7 Agonist GS-9620 Is a Potent Inhibitor of Acute HIV-1 Infection in Human Peripheral Blood Mononuclear Cells"],"prefix":"10.1128","volume":"61","author":[{"given":"Rujuta A.","family":"Bam","sequence":"first","affiliation":[{"name":"Department of Biology, Gilead Sciences, Inc., Foster City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Biology, Gilead Sciences, Inc., Foster City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alivelu","family":"Irrinki","sequence":"additional","affiliation":[{"name":"Department of Biology, Gilead Sciences, Inc., Foster City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Mulato","sequence":"additional","affiliation":[{"name":"Department of Biology, Gilead Sciences, Inc., Foster City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregg S.","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Biology, Gilead Sciences, Inc., Foster City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Hesselgesser","sequence":"additional","affiliation":[{"name":"Department of Biology, Gilead Sciences, Inc., Foster City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian R.","family":"Frey","sequence":"additional","affiliation":[{"name":"Department of Biology, Gilead Sciences, Inc., Foster City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Cihlar","sequence":"additional","affiliation":[{"name":"Department of Biology, Gilead Sciences, Inc., Foster City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen R.","family":"Yant","sequence":"additional","affiliation":[{"name":"Department of Biology, Gilead Sciences, Inc., Foster City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)01201-1"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00079"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4889(01)00182-3"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.6.863"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.9.4531"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.08.012"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0802257"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2010.06.001"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20021633"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.3.1551"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001999"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1089\/aid.2008.0303"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00027-06"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.21.120601.141126"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1089\/aid.2012.0313"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.5.2888"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.113.207878"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm400815m"},{"key":"e_1_3_2_20_2","volume-title":"Abstr 22nd Annu Conf Retrovir Opportunist Infect","author":"Sloan DD","year":"2015","unstructured":"Sloan DD IrrinkiATsaiAKaurJLalezariJMurryJCihlarT. 2015. 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