title: Naturally occurring compounds elicit HIV-1 replication in chronically infected promonocytic cells.
abstract: Since antiretroviral therapy suppresses but does not eradicate HIV-1 infection, methods to purge viral reservoirs are required. Many strategies involve the reactivation of chronically HIV infected cells to induce the expression of integrated viral genome. In this study, five bioactive compounds, the plant derivatives 1-cinnamoyl-3,11-dihydroxymeliacarpin (CDM), nordihydroguaiaretic acid (NDGA), and curcumin (Cur) and the synthetic stigmasterol analogs (22S,23S)-22,23-dihydroxystigmast-4-en-3-one (compound 1) and (22S,23S)-3 β -bromo-5 α ,22,23-trihydroxystigmastan-6-one (compound 2), were evaluated for their ability to elicit HIV replication in promonocytic (U1) and lymphocytic (H9+) HIV-1 chronically infected cells. The results revealed that natural compounds CDM, NDGA, and Cur were able to increase HIV-1 p24 antigen, determined by ELISA, only in latently infected promonocytic cells. CDM would reactivate HIV from latency by modulating the release of IL-6 and TNF- α , since the amount of both cytokines measured through ELISA significantly increased in U1 treated cells. Besides, NDGA increased ROS production, which might be related to the increase on p24 level observed in NDGA treated U1. These findings suggest that CDM, NDGA, and Cur might be candidates for further studies on latency-reversing therapeutics to eliminate latently HIV-1 reservoirs.
authors.affiliation: Laboratory of Virology, Department of Biological Chemistry, IQUIBICEN, School of Science, University of Buenos Aires, Ciudad Universitaria, Pabellón 2, 4to. Piso, Intendente Güiraldes 2160, C1428EGA Buenos Aires, Argentina.
authors.forename: Andrea Alejandra
authors.initials: AA
authors.lastname: Barquero
authors.affiliation: Laboratory of Virology, Department of Biological Chemistry, IQUIBICEN, School of Science, University of Buenos Aires, Ciudad Universitaria, Pabellón 2, 4to. Piso, Intendente Güiraldes 2160, C1428EGA Buenos Aires, Argentina.
authors.forename: María Eugenia
authors.initials: ME
authors.lastname: Dávola
authors.affiliation: Laboratory of Virology, Department of Biological Chemistry, IQUIBICEN, School of Science, University of Buenos Aires, Ciudad Universitaria, Pabellón 2, 4to. Piso, Intendente Güiraldes 2160, C1428EGA Buenos Aires, Argentina.
authors.forename: Diego Ariel
authors.initials: DA
authors.lastname: Riva
authors.affiliation: Laboratory of Virology, Department of Biological Chemistry, IQUIBICEN, School of Science, University of Buenos Aires, Ciudad Universitaria, Pabellón 2, 4to. Piso, Intendente Güiraldes 2160, C1428EGA Buenos Aires, Argentina.
authors.forename: Susana Esther
authors.initials: SE
authors.lastname: Mersich
authors.affiliation: Laboratory of Virology, Department of Biological Chemistry, IQUIBICEN, School of Science, University of Buenos Aires, Ciudad Universitaria, Pabellón 2, 4to. Piso, Intendente Güiraldes 2160, C1428EGA Buenos Aires, Argentina.
authors.forename: Laura Edith
authors.initials: LE
authors.lastname: Alché
mesh_terms: D001685:Biological Factors / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D002778:Cholestanones / Q000494:pharmacology; D003474:Curcumin / Q000494:pharmacology; D004261:DNA Replication / Q000187:drug effects; D015658:HIV Infections / Q000378:metabolism / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D036701:Limonins / Q000494:pharmacology; D009637:Masoprocol / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism / Q000821:virology*; D010936:Plant Extracts / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013265:Stigmasterol / Q000031:analogs & derivatives / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D020298:U937 Cells; D014779:Virus Replication / Q000187:drug effects*
chemical_list: C474472:1-cinnamoyl-3,11-dihydroxymeliacarpin; C581395:22,23-dihydroxystigmast-4-en-3-one; C493970:3-bromo-5,22,23-trihydroxystigmastan-6-one; D001685:Biological Factors; D002778:Cholestanones; D015850:Interleukin-6; D036701:Limonins; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D009637:Masoprocol; D013265:Stigmasterol; D003474:Curcumin