Intervirology, 2013, 01, 242─248

Histonedeactylase inhibitor SAHA inducesa synergistic HIV-1 reactivation by TPA in latently infected cells

SoonYoung Park, KyungChang Kim, KeeJong Hong, Sung Soon Kim and ByeongSun Choi

Abstract

Objectives: 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 TM 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.

• ISBN or ISSN: 0300-5526

• 본 연구는 질병관리본부 연구개발과제(과제번호 2010-N51001-00) 연구비를 지원받아 수행되었습니다.
• This research was supported by a fund(code 2010-N51001-00) by Research of Korea Centers for Disease Control and Prevention.