The novel histone deacetylase inhibitors metacept-1 and metacept-3 potently increase HIV-1 transcription in latently infected cells.
We investigated the ability of several novel class I histone deacetylase inhibitors to activate HIV-1 transcription in latently infected cell lines. Oxamflatin, metacept-1 and metacept-3 induced high levels of HIV-1 transcription in latently infected T cell and monocytic cells lines, were potent inhibitors of histone deacetylase activity and caused preferential cell death in transcriptionally active cells. Although these compounds had potent in-vitro activity, their cytotoxicity may limit their use in patients.
Shehu-Xhilaga
Miranda
M
Infectious Diseases Unit, Alfred Hospital, Melbourne, Victoria, Australia.
Rhodes
David
D
Wightman
Fiona
F
Liu
Hong B
HB
Solomon
Ajantha
A
Saleh
Suha
S
Dear
Anthony E
AE
Cameron
Paul U
PU
Lewin
Sharon R
SR
D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D004353:Drug Evaluation, Preclinical / Q000379:methods; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000821:virology*; D015533:Transcriptional Activation / Q000187:drug effects*; D017735:Virus Latency / Q000187:drug effects
D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D013449:Sulfonamides; C527236:metacept-1; C100692:oxamflatin; D006655:Histone Deacetylases