title: Histone deactylase inhibitor SAHA induces a synergistic HIV-1 reactivation by 12-O-tetradecanoylphorbol-13-acetate in latently infected cells.
abstract: OBJECTIVE
  Recent studies have reported that human immunodeficiency virus type 1 (HIV-1) proviruses are strongly suppressed in the unique epigenetic environments caused by chromatin modifications such as acetylation and methylation. Therefore, optimized therapeutic strategies directed against the virus reservoir using these epigenetic modifying agents (EMAs) should cure HIV infection.
  
  
  METHODS
  Cytotoxicity and HIV-1 reactivation were determined using the PrestoBlue™ Cell Viability Reagent and p24 HIV ELISA, respectively.
  
  
  RESULTS
  EMAs, including histone deacetylase inhibitors (VPA and SAHA), DNA methyltransferase inhibitor (5'-Aza-CdR), histone methyltransferase inhibitor (ADOX) and 12-O-tetradecanoylphorbol-13-acetate (TPA), were used to reactivate proviruses in HIV-1 latently infected cells. The effect of monotreatment with these EMAs on HIV-1 reactivation was VPA or SAHA > 5'-Aza-CdR > ADOX. Even though cotreatment with these potential HIV-1 reactivating agents did not show any significant reactivation effects in HIV-1 latently infected cells, employing SAHA under TPA treatment demonstrated a dramatic synergistic effect on purging HIV-1 proviruses in all HIV-1 latently infected cells via the ERK and AP-1 pathways.
  
  
  CONCLUSIONS
  These results suggest that the combined approaches of EMAs, cotreatment of SAHA and TPA, could provide an effective way to lead a decline of HIV-1 reservoirs in patients.
authors.affiliation: Division of AIDS, Center for Immunology and Pathology, Korea National Institute of Health, Chungbuk, Republic of Korea.
authors.forename: Soon Young
authors.initials: SY
authors.lastname: Park
authors.forename: Kyung-Chang
authors.initials: KC
authors.lastname: Kim
authors.forename: Kee-Jong
authors.initials: KJ
authors.lastname: Hong
authors.forename: Sung Soon
authors.initials: SS
authors.lastname: Kim
authors.forename: Byeong-Sun
authors.initials: BS
authors.lastname: Choi
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D016655:HIV Core Protein p24 / Q000032:analysis; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D056572:Histone Deacetylase Inhibitors / Q000378:metabolism*; D006801:Humans; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives* / Q000378:metabolism; D014775:Virus Activation / Q000187:drug effects*; D017735:Virus Latency / Q000187:drug effects*
chemical_list: C554292:12-O-tetradecanoylphorbol-1,3-acetate; D016655:HIV Core Protein p24; D056572:Histone Deacetylase Inhibitors; D013755:Tetradecanoylphorbol Acetate