Read by QxMD icon Read

Hdac hiv

Christopher J Millard, Peter J Watson, Louise Fairall, John W R Schwabe
Histone deacetylase (HDAC) inhibitors are proven anticancer therapeutics and have potential in the treatment of many other diseases including HIV infection, Alzheimer's disease, and Friedreich's ataxia. A problem with the currently available HDAC inhibitors is that they have limited specificity and target multiple deacetylases. Designing isoform-selective inhibitors has proven challenging due to similarities in the structure and chemistry of HDAC active sites. However, the fact that HDACs 1, 2, and 3 are recruited to several large multi-subunit complexes, each with particular biological functions, raises the possibility of specifically inhibiting individual complexes...
January 27, 2017: Trends in Pharmacological Sciences
Yoshifumi Kobayashi, Céline Gélinas, Joseph P Dougherty
Antiretroviral therapy (ART) can control HIV-1 replication in infected individuals. Unfortunately, patients remain persistently infected owing to the establishment of latent infection requiring that ART be maintained indefinitely. One strategy being pursued involves the development of latency reversing agents (LRAs) to eliminate the latent arm of the infection. One class of molecules that has been tested for LRA activity is the epigenetic modulating compounds histone deacetylases inhibitors (HDACis). Previously, initial screening of these molecules typically commenced using established cell models of viral latency, and although certain drugs such as the HDACi SAHA demonstrated strong activity in these models, it did not translate to comparable activity with patient samples...
January 22, 2017: Journal of General Virology
Yasuko Tsunetsugu-Yokota, Mie Kobayahi-Ishihara, Yamato Wada, Kazutaka Terahara, Haruko Takeyama, Ai Kawana-Tachikawa, Kenzo Tokunaga, Makoto Yamagishi, Javier P Martinez, Andreas Meyerhans
Homeostatic proliferation (HSP) is a major mechanism by which long-lived naïve and memory CD4(+) T cells are maintained in vivo and suggested to contribute to the persistence of the latent HIV-1 reservoir. However, while many in vitro latency models rely on CD4(+) T cells that were initially differentiated via T-cell receptor (TCR) stimulation into memory/effector cells, latent infection of naïve resting CD4(+) T cells maintained under HSP conditions has not been fully addressed. Here, we describe an in vitro HSP culture system utilizing the cytokines IL-7 and IL-15 that allows studying latency in naïve resting CD4(+) T cells...
2016: Frontiers in Microbiology
Zhujun Ao, Rong Zhu, Xiaoli Tan, Lisa Liu, Liyu Chen, Shuiping Liu, XiaoJian Yao
BACKGROUND: HIV-1 latency is a major obstacle for HIV-1 eradication. Extensive efforts are being directed toward the reactivation of latent HIV reservoirs with the aim of eliminating latently infected cells via the host immune system and/or virus-mediated cell lysis. RESULTS: We screened over 1,500 small molecules and kinase inhibitors and found that a small molecule, PKC412 (midostaurin, a broad-spectrum kinase inhibitor), can stimulate viral transcription and expression from the HIV-1 latently infected ACH2 cell line and primary resting CD4+ T cells...
October 21, 2016: Virology Journal
Makoto Isono, Akinori Sato, Kazuki Okubo, Takako Asano, Tomohiko Asano
The histone deacetylase (HDAC) inhibitor belinostat increases the amount of unfolded proteins in cells by promoting the acetylation of heat shock protein 90 (HSP90), thereby disrupting its chaperone function. The human immunodeficiency virus protease inhibitor ritonavir, on the other hand, not only increases unfolded proteins by suppressing HSP90 but also acts as a proteasome inhibitor. We thought that belinostat and ritonavir together would induce endoplasmic reticulum (ER) stress and kill renal cancer cells effectively...
2016: Oncology Research
Hoyong Lim, Kyung-Chang Kim, Junseock Son, Younghyun Shin, Cheol-Hee Yoon, Chun Kang, Byeong-Sun Choi
HIV-1 reservoirs remain a major barrier to HIV-1 eradication. Although combination antiretroviral therapy (cART) can successfully reduce viral replication, it cannot reactivate HIV-1 provirus in this reservoir. Therefore, HIV-1 provirus reactivation strategies by cell activation or epigenetic modification are proposed for the eradication of HIV-1 reservoirs. Although treatment with the protein kinase A (PKA) activator cyclic AMP (cAMP) or epigenetic modifying agents such as histone deacetylase inhibitors (HDACi) alone can induce HIV-1 reactivation in latently infected cells, the synergism of these agents has not been fully evaluated...
January 2, 2017: Virus Research
Andrew J Yee, William I Bensinger, Jeffrey G Supko, Peter M Voorhees, Jesus G Berdeja, Paul G Richardson, Edward N Libby, Ellen E Wallace, Nicole E Birrer, Jill N Burke, David L Tamang, Min Yang, Simon S Jones, Catherine A Wheeler, Robert J Markelewicz, Noopur S Raje
BACKGROUND: Histone deacetylase (HDAC) inhibitors are an important new class of therapeutics for treating multiple myeloma. Ricolinostat (ACY-1215) is the first oral selective HDAC6 inhibitor with reduced class I HDAC activity to be studied clinically. Motivated by findings from preclinical studies showing potent synergistic activity with ricolinostat and lenalidomide, our goal was to assess the safety and preliminary activity of the combination of ricolinostat with lenalidomide and dexamethasone in relapsed or refractory multiple myeloma...
November 2016: Lancet Oncology
Bizhan Romani, Razieh Kamali Jamil, Mojtaba Hamidi-Fard, Pooneh Rahimi, Seyed Bahman Momen, Mohammad Reza Aghasadeghi, Elham Allahbakhshi
HIV-1 Vpr is an accessory protein that induces proteasomal degradation of multiple proteins. We recently showed that Vpr targets class I HDACs on chromatin for proteasomal degradation. Here we show that Vpr induces degradation of HDAC1 and HDAC3 in HIV-1 latently infected J-Lat cells. Degradation of HDAC1 and HDAC3 was also observed on the HIV-1 LTR and as a result, markers of active transcription were recruited to the viral promoter and induced viral activation. Knockdown of HDAC1 and HDAC3 activated the latent HIV-1 provirus and complementation with HDAC3 inhibited Vpr-induced HIV-1 reactivation...
2016: Scientific Reports
Victoria E Walker-Sperling, Christopher W Pohlmeyer, Patrick M Tarwater, Joel N Blankson
Shock and kill strategies involving the use of small molecules to induce viral transcription in resting CD4+ T cells (shock) followed by immune mediated clearance of the reactivated cells (kill), have been proposed as a method of eliminating latently infected CD4+ T cells. The combination of the histone deacetylase (HDAC) inhibitor romidepsin and protein kinase C (PKC) agonist bryostatin-1 is very effective at reversing latency in vitro. However, we found that primary HIV-1 specific CD8+ T cells were not able to eliminate autologous resting CD4+ T cells that had been reactivated with these drugs...
June 2016: EBioMedicine
Muna Ali Abdalla
Bioactive natural products are serendipitous drug candidates, which stimulate synthetic approaches for improving and supporting drug discovery and development. Therefore, the search for bioactive metabolites from different natural sources continues to play an important role in fashioning new medicinal agents. Several cyclic peptides were produced by organisms, such as β-defensins, gramicidin S, and tyrocidine A, and exhibited a wide range of bioactivities, such as antiviral activity against HIV-1, influenza A viruses, or antibacterial activity...
October 2016: Journal of Natural Medicines
Jun Li, Cancan Chen, Xiancai Ma, Guannan Geng, Bingfeng Liu, Yijun Zhang, Shaoyang Zhang, Fudi Zhong, Chao Liu, Yue Yin, Weiping Cai, Hui Zhang
Long noncoding RNAs (lncRNAs) play multiple key regulatory roles in various cellular pathways. However, their functions in HIV-1 latent infection remain largely unknown. Here we show that a lncRNA named NRON, which is highly expressed in resting CD4(+) T lymphocytes, could be involved in HIV-1 latency by specifically inducing Tat protein degradation. Our results suggest that NRON lncRNA potently suppresses the viral transcription by decreasing the cellular abundance of viral transactivator protein Tat. NRON directly links Tat to the ubiquitin/proteasome components including CUL4B and PSMD11, thus facilitating Tat degradation...
June 13, 2016: Nature Communications
Farhad B Hashemi, Kris Barreto, Wendy Bernhard, Pargol Hashemi, Adam Lomness, Ivan Sadowski
UNLABELLED: Understanding the mechanisms of HIV proviral latency is essential for development of a means to eradicate infection and achieve a cure. We have previously described an in vitro latency model that reliably identifies HIV expression phenotypes of infected cells using a dual-fluorescence reporter virus. Our results have demonstrated that ∼50% of infected cells establish latency immediately upon integration of provirus, a phenomenon termed early latency, which appears to occur by mechanisms that are distinct from epigenetic silencing observed with HIV provirus that establishes productive infections...
June 1, 2016: Journal of Virology
Jessica M Mates, Suresh de Silva, Mark Lustberg, Kelsey Van Deusen, Robert A Baiocchi, Li Wu, Jesse J Kwiek
Human immunodeficiency virus type 1 (HIV-1) latency is a major barrier to a cure of AIDS. Latently infected cells harbor an integrated HIV-1 genome but are not actively producing HIV-1. Histone deacetylase (HDAC) inhibitors, such as vorinostat (SAHA), have been shown to reactivate latent HIV-1. AR-42, a modified HDAC inhibitor, has demonstrated efficacy against malignant melanoma, meningioma, and acute myeloid leukemia and is currently used in clinical trials for non-Hodgkin's lymphoma and multiple myeloma...
2015: Retrovirology: Research and Treatment
Tara Hurst, Matthew Pace, Aris Katzourakis, Rodney Phillips, Paul Klenerman, John Frater, Gkikas Magiorkinis
BACKGROUND: While antiretroviral therapies have improved life expectancy and reduced viral loads in HIV-1-positive individuals, the cessation of treatment results in a rebound of viral replication. This suggests that a reservoir of latently-infected cells remains within these patients, the identity of which is ill-defined and therefore difficult to target therapeutically. Current strategies are aimed at using drugs such as histone deacetylase (HDAC) inhibitors to induce the expression of latent HIV-1 proviruses in order to activate and ultimately eradicate this reservoir of infected cells...
February 6, 2016: Retrovirology
Md Saha Jamaluddin, Pei-Wen Hu, Yih Jan, Edward B Siwak, Andrew P Rice
Cessation of highly active antiretroviral therapy (HAART) in HIV-infected individual leads to a rebound of viral replication due to reactivation of a viral reservoir composed largely of latently infected memory CD4(+) T cells. Efforts to deplete this reservoir have focused on reactivation of transcriptionally silent latent proviruses. HIV provirus transcription depends critically on the positive transcription elongation factor b (P-TEFb), whose core components are cyclin-dependent kinase 9 (CDK9) and cyclin T1...
February 2016: AIDS Research and Human Retroviruses
Ane Bjerg Christensen, Anders Dige, Johan Vad-Nielsen, Christel R Brinkmann, Mia Bendix, Lars Østergaard, Martin Tolstrup, Ole S Søgaard, Thomas A Rasmussen, Jens Randel Nyengaard, Jørgen Agnholt, Paul W Denton
Intestinal CD4(+) T cell depletion is rapid and profound during early HIV-1 infection. This leads to a compromised mucosal barrier that prompts chronic systemic inflammation. The preferential loss of intestinal T helper 17 (Th17) cells in HIV-1 disease is a driver of the damage within the mucosal barrier and of disease progression. Thus, understanding the effects of new therapeutic strategies in the intestines has high priority. Histone deacetylase (HDAC) inhibitors (e.g., panobinostat) are actively under investigation as potential latency reversing agents in HIV eradication studies...
2015: Mediators of Inflammation
Bizhan Romani, Nima Shaykh Baygloo, Mojtaba Hamidi-Fard, Mohammad Reza Aghasadeghi, Elham Allahbakhshi
Mechanisms underlying HIV-1 latency remain among the most crucial questions that need to be answered to adopt strategies for purging the latent viral reservoirs. Here we show that HIV-1 accessory protein Vpr induces depletion of class I HDACs, including HDAC1, 2, 3, and 8, to overcome latency in macrophages. We found that Vpr binds and depletes chromatin-associated class I HDACs through a VprBP-dependent mechanism, with HDAC3 as the most affected class I HDAC. De novo expression of Vpr in infected macrophages induced depletion of HDAC1 and 3 on the HIV-1 LTR that was associated with hyperacetylation of histones on the HIV-1 LTR...
February 5, 2016: Journal of Biological Chemistry
Thijs Booiman, Vladimir V Loukachov, Karel A van Dort, Angélique B van 't Wout, Neeltje A Kootstra
BACKGROUND: Transcription of the HIV-1 provirus is regulated by both viral and host proteins and is very important in the context of viral latency. In latently infected cells, viral gene expression is inhibited as a result of the sequestration of host transcription factors and epigenetic modifications. RESULTS: In our present study we analyzed the effect of host factor dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) on HIV-1 replication. We show that DYRK1A controls HIV-1 replication by regulating provirus transcription...
2015: PloS One
Xiaolong Tang, Yong Liang, Xinkuang Liu, Shuping Zhou, Liang Liu, Fujina Zhang, Chunmei Xie, Shuyu Cai, Jia Wei, Yongqiang Zhu, Wei Hou
Activating HIV-1 proviruses in latent reservoirs combined with inhibiting viral spread might be an effective anti-HIV therapeutic strategy. Active specific delivery of therapeutic drugs into cells harboring latent HIV, without the use of viral vectors, is a critical challenge to this objective. In this study, nanoparticles of poly(lactic-co-glycolic acid)-polyethylene glycol diblock copolymers conjugated with anti-CD45RO antibody and loaded with the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) and/or protease inhibitor nelfinavir (Nel) were tested for activity against latent virus in vitro...
December 2015: Nanoscale Research Letters
Kenichi Imai, Takashi Okamoto, Kuniyasu Ochiai
BACKGROUND/AIMS: The ability of human immunodeficiency virus-1(HIV-1) to establish latent infection and its re-activation is considered critical for progression of HIV-1 infection. We previously reported that a bacterial metabolite butyric acid, acting as a potent inhibitor of histone deacetylases (HDACs), could lead to induction of HIV-1 transcription; however, the molecular mechanism remains unclear. The aim of this study was to investigate the effect of butyric acid on HIV-1 gene expression...
2015: Cellular Physiology and Biochemistry
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"