%0 Journal Article
%T Latent HIV in primary T lymphocytes is unresponsive to histone deacetylase inhibitors
%A Gautam K Sahu
%A Miles W Cloyd
%J Virology Journal
%D 2011
%I BioMed Central
%R 10.1186/1743-422x-8-400
%X The presence of resting memory CD4 T lymphocytes that harbor chromosomally integrated latent HIVs has been one of the major obstacles in eliminating HIV from patients using HAART [1,2]. Although the frequencies of these cells in vivo are very low (i.e., ~1-10 latently infected cells per million CD4 T cells), these highly stable cells serve as a life-long reservoir for HIV in infected individuals, despite long-term effective therapy [3]. To attain an eventual cure for HIV, if ever achievable, the elimination of these cells from patients is necessary, which remains extremely challenging and it is not clear how that can be achieved.The mechanisms involved in HIV latency are multifactorial [4] and one of the underlying mechanisms found for the maintenance of latent HIV in transformed cell lines is the chromatin-mediated suppression of viral mRNA synthesis from the HIV LTR [5]. The treatment of latently infected cell lines with HDAC inhibitors, such as valproic acid (VPA) or trichostatin A (TSA), can increase the levels of histone acetylation [6,7], leading to changes in local chromatin organization at the latent HIV LTR [8-10]. This disruption of compact chromatin structure at the LTR causes higher levels of HIV transcription, resulting in the reactivation of latent HIV [10] and production of viral progeny in cell lines. Therefore, recent thrusts in the field are to identify potent HDAC inhibitors and use them clinically, because the assumption is that once HDAC inhibitors reactivate latent HIVs in resting CD4 T cells in patients, these cells will die because of virus-induced cytopathicity and/or HIV-specific cell-mediated immunity which is present. However, it is not entirely clear if these drugs can stimulate latent HIVs in primary CD4 T cells.We have previously shown the formation of latent HIV at high-percentages in HIV-infected primary CD4 T cells in vitro using a feeder cell line, H80 [11], to keep the lymphocytes alive and healthy. Here, we have tested whether va
%U http://www.virologyj.com/content/8/1/400