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• W2947382672 abstract "Despite the success of antiretroviral therapy (ART), eradication of HIV-1 from brain reservoirs remains elusive. HIV-1 brain reservoirs include perivascular macrophages that are behind the blood-brain barrier and difficult to access by ART. Macrophages express transcription factor FOXO3a and the TNF superfamily cytokine TRAIL, which are known to target HIV-1-infected macrophages for viral inhibition. ONC201 is a novel and potent FOXO3a activator capable of inducing TRAIL. It can cross the blood-brain barrier, and has shown antitumor effects in clinical trials. We hypothesized that activation of FOXO3a/TRAIL by ONC201 will inhibit HIV-1 replication in macrophages. Using primary human monocyte-derived macrophages, we demonstrated that ONC201 dose-dependently decreased replication levels of both HIV-1 laboratory strain and primary strains as determined by HIV-1 reverse transcriptase activity assay. Consistent with data on HIV-1 replication, ONC201 also reduced intracellular and extracellular p24, viral RNA, and integrated HIV-1 DNA in infected macrophages. Blocking TRAIL or knockdown of FOXO3a with siRNA reversed ONC201-mediated HIV-1 suppression, suggesting that ONC201 inhibits HIV-1 through FOXO3a and TRAIL. The anti-HIV-1 effect of ONC201 was further validated in vivo in NOD/scid-IL-2Rgcnull mice. After intracranial injection of HIV-1-infected macrophages into the basal ganglia, we treated the mice daily with ONC201 through intraperitoneal injection for six days. ONC201 significantly decreased p24 levels in both the macrophages and the brain tissues, suggesting that ONC201 suppresses HIV-1 in vivo. Therefore, ONC201 can be a promising drug candidate to combat persistent HIV-1 infection in the brain." @default.
• W2947382672 created "2019-06-07" @default.
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• W2947382672 date "2019-08-01" @default.
• W2947382672 modified "2023-10-17" @default.
• W2947382672 title "Small molecule ONC201 inhibits HIV-1 replication in macrophages via FOXO3a and TRAIL" @default.
• W2947382672 cites W1524482777 @default.
• W2947382672 cites W1545961146 @default.
• W2947382672 cites W1549386419 @default.
• W2947382672 cites W1554892411 @default.
• W2947382672 cites W1647734909 @default.
• W2947382672 cites W1969202617 @default.
• W2947382672 cites W1971112771 @default.
• W2947382672 cites W1975258429 @default.
• W2947382672 cites W1984811742 @default.
• W2947382672 cites W1987038702 @default.
• W2947382672 cites W1995638825 @default.
• W2947382672 cites W1999083565 @default.
• W2947382672 cites W2002254372 @default.
• W2947382672 cites W2007530728 @default.
• W2947382672 cites W2016329566 @default.
• W2947382672 cites W2017749679 @default.
• W2947382672 cites W2033561793 @default.
• W2947382672 cites W2034071655 @default.
• W2947382672 cites W2035036667 @default.
• W2947382672 cites W2036890038 @default.
• W2947382672 cites W2037978214 @default.
• W2947382672 cites W2048646138 @default.
• W2947382672 cites W2050693077 @default.
• W2947382672 cites W2051546740 @default.
• W2947382672 cites W2055796578 @default.
• W2947382672 cites W2056217426 @default.
• W2947382672 cites W2059724105 @default.
• W2947382672 cites W2060116181 @default.
• W2947382672 cites W2073836757 @default.
• W2947382672 cites W2081273376 @default.
• W2947382672 cites W2084373412 @default.
• W2947382672 cites W2090720637 @default.
• W2947382672 cites W2092508425 @default.
• W2947382672 cites W2093106975 @default.
• W2947382672 cites W2096141271 @default.
• W2947382672 cites W2105186639 @default.
• W2947382672 cites W2107250683 @default.
• W2947382672 cites W2111364281 @default.
• W2947382672 cites W2113002082 @default.
• W2947382672 cites W2115978863 @default.
• W2947382672 cites W2117087670 @default.
• W2947382672 cites W2117963070 @default.
• W2947382672 cites W2119019497 @default.
• W2947382672 cites W2124114936 @default.
• W2947382672 cites W2130988210 @default.
• W2947382672 cites W2133315239 @default.
• W2947382672 cites W2135547889 @default.
• W2947382672 cites W2136318199 @default.
• W2947382672 cites W2140580240 @default.
• W2947382672 cites W2140712036 @default.
• W2947382672 cites W2143298530 @default.
• W2947382672 cites W2149584931 @default.
• W2947382672 cites W2158867438 @default.
• W2947382672 cites W2159642096 @default.
• W2947382672 cites W2159999972 @default.
• W2947382672 cites W2162606162 @default.
• W2947382672 cites W2164713283 @default.
• W2947382672 cites W2231325109 @default.
• W2947382672 cites W2283948643 @default.
• W2947382672 cites W2287138409 @default.
• W2947382672 cites W2399570302 @default.
• W2947382672 cites W2489728460 @default.
• W2947382672 cites W2514974106 @default.
• W2947382672 cites W2600944061 @default.
• W2947382672 cites W2612676198 @default.
• W2947382672 cites W2613790813 @default.
• W2947382672 cites W2624701221 @default.
• W2947382672 cites W2754353621 @default.
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• W2947382672 cites W2773577558 @default.
• W2947382672 cites W2774292278 @default.
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• W2947382672 doi "https://doi.org/10.1016/j.antiviral.2019.05.015" @default.
• W2947382672 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6620139" @default.
• W2947382672 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31158413" @default.
• W2947382672 hasPublicationYear "2019" @default.
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