August 14, 2014
Previous studies have indicated that histone deacetylase (HDAC) inhibitors might be potential candidates in HIV cure strategies. As part of a "flush-and-kill" strategy, the hope was that HDAC inhibitors could expose virus hidden in the reservoirs, at which point cytotoxic T lymphocytes (CTLs), also known as killer T cells, could then eliminate the exposed virus.
However, HDAC inhibitors may actually suppress CTL activity, thereby compromising the "kill" part of the strategy, according to study results published in PLOS Pathogens.
At least three HDAC inhibitors -- romidepsin, panobinostat and vorinostat (SAHA) -- are currently being investigated as flushing agents. These HDAC inhibitors interact differently with the 18 known HDACs in the human body, and also interact with other immune cells.
"This high degree of complexity both in terms of immunological outcomes and underlying mechanisms, necessitates that HDAC inhibitors be studied in a context that is matched to their intended utility, said lead author Richard Brad Jones, Ph.D., from the Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard, in a press release.
Therefore, Jones and his team set out to see whether the three HDAC inhibitors affected the ability of CTLs to eliminate HIV-infected cells.
While the effects of each drug vary depending on the assays used, doses and schedules, all three HDAC inhibitors were found to impair the ability of CTLs to kill infected cells. Additionally, the drugs rapidly suppressed CTL production of a key immune mediator known as interferon gamma.
Because the tests were done using cell cultures, the extent to which HDAC inhibitors affect the CTL response in an HIV-infected patient remains to be seen. While more research needs to be done, the researchers caution that the immunosuppressive activity of the HDAC inhibitors that they observed should be taken into consideration by future studies.
Warren Tong is the research editor for TheBody.com and TheBodyPRO.com.
Follow Warren on Twitter: @WarrenAtTheBody.