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Epigenetics & HIV

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https://www.readbyqxmd.com/read/28246360/multiple-histone-lysine-methyltransferases-are-required-for-the-establishment-and-maintenance-of-hiv-1-latency
#1
Kien Nguyen, Biswajit Das, Curtis Dobrowolski, Jonathan Karn
We showed previously that the histone lysine methyltransferase (HKMT) H3K27me3 (EZH2) is the catalytic subunit of Polycomb repressive complex 2 (PRC2) and is required for the maintenance of HIV-1 latency in Jurkat T cells. Here we show, by using chromatin immunoprecipitation experiments, that both PRC2 and euchromatic histone-lysine N-methyltransferase 2 (EHMT2), the G9a H3K9me2-3 methyltransferase, are highly enriched at the proviral 5' long terminal repeat (LTR) and rapidly displaced upon proviral reactivation...
February 28, 2017: MBio
https://www.readbyqxmd.com/read/28187462/recombinant-tat-bmi-1-fusion-protein-induces-ex-vivo-expansion-of-human-umbilical-cord-blood-derived-hematopoietic-stem-cells
#2
Bruna Codispoti, Nicola Rinaldo, Emanuela Chiarella, Michela Lupia, Cristina Barbara Spoleti, Maria Grazia Marafioti, Annamaria Aloisio, Stefania Scicchitano, Marco Giordano, Giovanna Nappo, Valeria Lucchino, Malcolm A S Moore, Pengbo Zhou, Maria Mesuraca, Heather Mandy Bond, Giovanni Morrone
Transplantation of hematopoietic stem cells (HSCs) is a well-established therapeutic approach for numerous disorders. HSCs are typically derived from bone marrow or peripheral blood after cytokine-induced mobilization. Umbilical cord blood (CB) represents an appealing alternative HSC source, but the small amounts of the individual CB units have limited its applications. The availability of strategies for safe ex vivo expansion of CB-derived HSCs (CB-HSCs) may allow to extend the use of these cells in adult patients and to avoid the risk of insufficient engraftment or delayed hematopoietic recovery...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28133810/systems-serology-for-evaluation-of-hiv-vaccine-trials
#3
REVIEW
Margaret E Ackerman, Dan H Barouch, Galit Alter
The scale and scope of the global epidemic, coupled to challenges with traditional vaccine development approaches, point toward a need for novel methodologies for HIV vaccine research. While the development of vaccines able to induce broadly neutralizing antibodies remains the ultimate goal, to date, vaccines continue to fail to induce these rare humoral immune responses. Conversely, growing evidence across vaccine platforms in both non-human primates and humans points to a role for polyclonal vaccine-induced antibody responses in protection from infection...
January 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28113052/hdac-inhibitors-containing-a-benzamide-functional-group-and-a-pyridyl-cap-are-preferentially-effective-hiv-1-latency-reversing-agents-in-primary-resting-cd4-t-cells
#4
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
https://www.readbyqxmd.com/read/27941949/in-vitro-effects-of-the-small-molecule-protein-kinase-c-agonists-on-hiv-latency-reactivation
#5
Jessica Brogdon, Widade Ziani, Xiaolei Wang, Ronald S Veazey, Huanbin Xu
The persistence of latently HIV-infected cellular reservoirs represents the major obstacle to virus eradication in patients under antiretroviral therapy (ART). Cure strategies to eliminate these reservoirs are thus needed to reactivate proviral gene expression in latently infected cells. In this study, we tested optimal concentrations of PKC agonist candidates (PEP005/Ingenol-3-angelate, prostratin, bryostatin-1, and JQ1) to reactivate HIV latency in vitro, and examined their effects on cell survival, activation and epigenetic histone methylation after treatment alone or in combination in cell line and isolated CD4 T cells from SIV-infected macaques...
December 12, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27922854/identification-of-hiv-infection-related-dna-methylation-sites-and-advanced-epigenetic-aging-in-hiv-positive-treatment-naive-u-s-veterans
#6
Kristin N Nelson, Qin Hui, David Rimland, Ke Xu, Matthew S Freiberg, Amy C Justice, Vincent C Marconi, Yan V Sun
OBJECTIVE: HIV-positive individuals are at higher risk than healthy persons for aging-related diseases, including myocardial infarction and non-AIDS defining cancers. Recent evidence suggests that HIV infection may modulate changes in the host cell epigenome, and these changes represent a potential mechanism through which HIV infection accelerates aging. We assessed the difference in DNA methylation (DNAm) age, an aging marker involving multiple age-related cytosine-guanine dinucleotide (CpG) sites, among antiretroviral treatment (ART)-naive HIV-positive and HIV-negative individuals in a cohort of veterans from the Veterans Aging Cohort Study...
February 20, 2017: AIDS
https://www.readbyqxmd.com/read/27800606/promoting-cancer-control-in-africa-with-ubuntu-a-report-of-the-african-organization-for-research-and-training-in-africa-aortic-10-th-conference-2015-in-marrakech-morocco
#7
Kenneth O Simbiri, Christopher K Williams, Marcella Macaluso, Antonio Giordano
The objectives of the African Organization for Research and Training in Cancer (AORTIC), includes bringing products of decades of advances in cancer research to African populations through local and international collaboration. The consistent and huge growth in participation in the conferences and the diversity of the nations is a witness to the success of the organization thus far. The theme for the Tenth AORTIC International Conference on Cancer in Africa in Morocco in 2015 was "Road map to Cancer Control in Africa" and topics of discussion of paramount importance for low- and middle-income African countries included childhood cancers such as BL, cancers of the cervix, breast, and prostate; cancers associated with HIV-infection such as cervical, vulvar, and anal; as well as cancer care challenges associated with palliative care...
November 1, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27763570/vitamin-d-status-and-its-consequences-for-health-in-south-africa
#8
REVIEW
Mary Norval, Anna K Coussens, Robert J Wilkinson, Liza Bornman, Robyn M Lucas, Caradee Y Wright
In this review, reports were retrieved in which vitamin D status, as assessed by serum 25-hydroxyvitamin D [25(OH)D] levels, was measured in South African population groups with varied skin colours and ethnicities. Healthy children and adults were generally vitamin D-sufficient [25(OH)D level >50 nmol/L] but the majority of those aged above 65 years were deficient. A major role for exposure to solar ultraviolet radiation (UVR) in determining 25(OH)D levels was apparent, with the dietary contribution being minor...
October 18, 2016: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/27756902/gene-expression-reversal-of-lncrnas-and-associated-mrnas-expression-in-active-vs-latent-hiv-infection
#9
Madhavan Nair, Vidya Sagar, Sudheesh Pilakka-Kanthikeel
Interplay between lncRNAs and mRNAs is rapidly emerging as a key epigenetic mechanism in controlling various cell functions. HIV can actively infect and/or can persist latently for years by manipulating host epigenetics; however, its molecular essence remains undiscovered in entirety. Here for the first time, we delineate the influence of HIV on global lncRNAs expression in monocytic cells lines. Our analysis revealed the expression modulation of nearly 1060 such lncRNAs which are associated with differentially expressed mRNAs in active and latent infection...
October 19, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27677464/synergistic-reactivation-of-latent-hiv-1-provirus-by-pka-activator-dibutyryl-camp-in-combination-with-an-hdac-inhibitor
#10
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
https://www.readbyqxmd.com/read/27672717/epigenome-wide-differential-dna-methylation-between-hiv-infected-and-uninfected-individuals
#11
Xinyu Zhang, Amy C Justice, Ying Hu, Zuoheng Wang, Hongyu Zhao, Guilin Wang, Eric O Johnson, Brinda Emu, Richard E Sutton, John H Krystal, Ke Xu
Epigenetic control of human immunodeficiency virus-1 (HIV-1) genes is critical for viral integration and latency. However, epigenetic changes in the HIV-1-infected host genome have not been well characterized. Here, we report the first large-scale epigenome-wide association study of DNA methylation for HIV-1 infection. We recruited HIV-infected (n = 261) and uninfected (n = 117) patients from the Veteran Aging Cohort Study (VACS) and all samples were profiled for 485,521 CpG sites in DNA extracted from the blood...
August 12, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27671333/utx-1-regulates-tat-induced-hiv-1-transactivation-via-changing-the-methylated-status-of-histone-h3
#12
Hong-Sheng Zhang, Guang-Yuan Du, Yang Liu, Zhong-Guo Zhang, Zhen Zhou, Hu Li, Ke-Qing Dai, Xiao-Ying Yu, Xiao-Meng Gou
Epigenetic modifications are thought to be important for gene expression changes during HIV-1 transcription and replication. The removal of histone H3 lysine27 (H3K27) trimethylation mark by UTX-1 is important for the robust induction of many specific genes during Tat-mediated HIV-1 transactvation. We found that UTX-1 enzymatic activity is needed for Tat to remove a repressive mark H3K27me3 in the HIV-1 long terminal repeat (LTR). UTX-1 converted the chromatin structure to a more transcriptionally active state by up-regulation of H3K4 methylation and down-regulation of H3K27 methylation on the specific regions of HIV-1 LTR...
September 23, 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27607592/cancer-therapies-in-hiv-cure-research
#13
Thomas A Rasmussen, Jenny L Anderson, Fiona Wightman, Sharon R Lewin
PURPOSE OF REVIEW: This article provides an overview of anticancer therapies in various stages of clinical development as potential interventions to target HIV persistence. RECENT FINDINGS: Epigenetic drugs developed for cancer have been investigated in vitro, ex vivo and in clinical trials as interventions aimed at reversing HIV latency and depleting the amount of virus that persists on antiretroviral therapy. Treatment with histone deacetylase inhibitors induced HIV expression in patients on antiretroviral therapy but did not reduce the frequency of infected cells...
January 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/27535703/hiv-and-cocaine-impact-glial-metabolism-energy-sensor-amp-activated-protein-kinase-role-in-mitochondrial-biogenesis-and-epigenetic-remodeling
#14
Thangavel Samikkannu, Venkata S R Atluri, Madhavan P N Nair
HIV infection and cocaine use have been identified as risk factors for triggering neuronal dysfunction. In the central nervous system (CNS), energy resource and metabolic function are regulated by astroglia. Glia is the major reservoir of HIV infection and disease progression in CNS. However, the role of cocaine in accelerating HIV associated energy deficit and its impact on neuronal dysfunction has not been elucidated yet. The aim of this study is to elucidate the molecular mechanism of HIV associated neuropathogenesis in cocaine abuse and how it accelerates the energy sensor AMPKs and its subsequent effect on mitochondrial oxidative phosphorylation (OXPHOS), BRSKs, CDC25B/C, MAP/Tau, Wee1 and epigenetics remodeling complex SWI/SNF...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27525044/restricting-retrotransposons-a-review
#15
REVIEW
John L Goodier
Retrotransposons have generated about 40 % of the human genome. This review examines the strategies the cell has evolved to coexist with these genomic "parasites", focussing on the non-long terminal repeat retrotransposons of humans and mice. Some of the restriction factors for retrotransposition, including the APOBECs, MOV10, RNASEL, SAMHD1, TREX1, and ZAP, also limit replication of retroviruses, including HIV, and are part of the intrinsic immune system of the cell. Many of these proteins act in the cytoplasm to degrade retroelement RNA or inhibit its translation...
2016: Mobile DNA
https://www.readbyqxmd.com/read/27519803/the-therapeutic-potential-of-epigenetic-manipulation-during-infectious-diseases
#16
Joby Cole, Paul Morris, Mark J Dickman, David H Dockrell
Epigenetic modifications are increasingly recognized as playing an important role in the pathogenesis of infectious diseases. They represent a critical mechanism regulating transcriptional profiles in the immune system that contributes to the cell-type and stimulus specificity of the transcriptional response. Recent data highlight how epigenetic changes impact macrophage functional responses and polarization, influencing the innate immune system through macrophage tolerance and training. In this review we will explore how post-translational modifications of histone tails influence immune function to specific infectious diseases...
November 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27401842/novel-epigenetic-changes-in-cdkn2a-are-associated-with-progression-of-cervical-intraepithelial-neoplasia
#17
N Ari Wijetunga, Thomas J Belbin, Robert D Burk, Kathleen Whitney, Maria Abadi, John M Greally, Mark H Einstein, Nicolas F Schlecht
OBJECTIVE: To conduct a comprehensive mapping of the genomic DNA methylation in CDKN2A, which codes for the p16(INK4A) and p14(ARF) proteins, and 14 of the most promising DNA methylation marker candidates previously reported to be associated with progression of low-grade cervical intraepithelial neoplasia (CIN1) to cervical cancer. METHODS: We analyzed DNA methylation in 68 HIV-seropositive and negative women with incident CIN1, CIN2, CIN3 and invasive cervical cancer, assaying 120 CpG dinucleotide sites spanning APC, CDH1, CDH13, CDKN2A, CDKN2B, DAPK1, FHIT, GSTP1, HIC1, MGMT, MLH1, RARB, RASSF1, TERT and TIMP3 using the Illumina Infinium array...
September 2016: Gynecologic Oncology
https://www.readbyqxmd.com/read/27381288/shutdown-of-hiv-1-transcription-in-t-cells-by-nullbasic-a-mutant-tat-protein
#18
Hongping Jin, Dongsheng Li, Haran Sivakumaran, Mary Lor, Lina Rustanti, Nicole Cloonan, Shivangi Wani, David Harrich
UNLABELLED: Nullbasic is a derivative of the HIV-1 transactivator of transcription (Tat) protein that strongly inhibits HIV-1 replication in lymphocytes. Here we show that lentiviral vectors that constitutively express a Nullbasic-ZsGreen1 (NB-ZSG1) fusion protein by the eEF1α promoter led to robust long-term inhibition of HIV-1 replication in Jurkat cells. Although Jurkat-NB-ZSG1 cells were infected by HIV-1, no virus production could be detected and addition of phorbol ester 12-myristate 13-acetate (PMA) and JQ1 had no effect, while suberanilohydroxamic acid (SAHA) modestly stimulated virus production but at levels 300-fold lower than those seen in HIV-1-infected Jurkat-ZSG1 cells...
2016: MBio
https://www.readbyqxmd.com/read/27359112/prenatal-exposures-and-dna-methylation-in-newborns-a-pilot-study-in-durban-south-africa
#19
Jaclyn M Goodrich, Poovendhree Reddy, Rajen N Naidoo, Kareshma Asharam, Stuart Batterman, Dana C Dolinoy
The in utero environment has the potential to influence epigenetic programming and subsequently the health of offspring. Even though pregnant women living in urban Africa are exposed to multiple chemicals and infectious agents that may impact their developing children, the neonatal epigenome has not been studied in these regions. We assessed whether prenatal exposures to air pollution and maternal human immunodeficiency virus (HIV) are associated with changes to DNA methylation throughout the epigenome using a pilot sample from the Mother and Child Environmental (MACE) birth cohort, of which 36% of the mothers are HIV positive...
July 13, 2016: Environmental Science. Processes & Impacts
https://www.readbyqxmd.com/read/27316325/impact-of-genetic-variations-in-c-c-chemokine-receptors-and-ligands-on-infectious-diseases
#20
REVIEW
Tabish Qidwai, M Y Khan
Chemokine receptors and ligands are crucial for extensive immune response against infectious diseases such as malaria, leishmaniasis, HIV and tuberculosis and a wide variety of other diseases. Role of chemokines are evidenced in the activation and regulation of immune cell migration which is important for immune response against diseases. Outcome of disease is determined by complex interaction among pathogen, host genetic variability and surrounding milieu. Variation in expression or function of chemokines caused by genetic polymorphisms could be associated with attenuated immune responses...
October 2016: Human Immunology
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