keyword
https://read.qxmd.com/read/37957382/viral-and-host-mediators-of-non-suppressible-hiv-1-viremia
#21
JOURNAL ARTICLE
Abbas Mohammadi, Behzad Etemad, Xin Zhang, Yijia Li, Gregory J Bedwell, Radwa Sharaf, Autumn Kittilson, Meghan Melberg, Charles R Crain, Anna K Traunbauer, Colline Wong, Jesse Fajnzylber, Daniel P Worrall, Alex Rosenthal, Hannah Jordan, Nikolaus Jilg, Clarety Kaseke, Francoise Giguel, Xiaodong Lian, Rinki Deo, Elisabeth Gillespie, Rida Chishti, Sara Abrha, Taylor Adams, Abigail Siagian, Dominic Dorazio, Peter L Anderson, Steven G Deeks, Michael M Lederman, Sigal Yawetz, Daniel R Kuritzkes, Mathias D Lichterfeld, Scott Sieg, Athe Tsibris, Mary Carrington, Zabrina L Brumme, Jose R Castillo-Mancilla, Alan N Engelman, Gaurav D Gaiha, Jonathan Z Li
Non-suppressible HIV-1 viremia (NSV) is defined as persistent low-level viremia on antiretroviral therapy (ART) without evidence of ART non-adherence or significant drug resistance. Unraveling the mechanisms behind NSV would broaden our understanding of HIV-1 persistence. Here we analyzed plasma virus sequences in eight ART-treated individuals with NSV (88% male) and show that they are composed of large clones without evidence of viral evolution over time in those with longitudinal samples. We defined proviruses that match plasma HIV-1 RNA sequences as 'producer proviruses', and those that did not as 'non-producer proviruses'...
December 2023: Nature Medicine
https://read.qxmd.com/read/37942865/neuro-hiv-new-insights-into-pathogenesis-and-emerging-therapeutic-targets
#22
JOURNAL ARTICLE
Dmitri Sviridov, Michael Bukrinsky
HIV-associated neurocognitive disorders (HAND) is a term describing a complex set of cognitive impairments accompanying HIV infection. Successful antiretroviral therapy (ART) reduces the most severe forms of HAND, but milder forms affect over 50% of people living with HIV (PLWH). Pathogenesis of HAND in the ART era remains unknown. A variety of pathogenic factors, such as persistent HIV replication in the brain reservoir, HIV proteins released from infected brain cells, HIV-induced neuroinflammation, and some components of ART, have been implicated in driving HAND pathogenesis in ART-treated individuals...
December 2023: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://read.qxmd.com/read/37922905/single-cell-epigenetic-transcriptional-and-protein-profiling-of-latent-and-active-hiv-1-reservoir-revealed-that-ikzf3-promotes-hiv-1-persistence
#23
JOURNAL ARTICLE
Yulong Wei, Timothy C Davenport, Jack A Collora, Haocong Katherine Ma, Delia Pinto-Santini, Javier Lama, Ricardo Alfaro, Ann Duerr, Ya-Chi Ho
Understanding how HIV-1-infected cells proliferate and persist is key to HIV-1 eradication, but the heterogeneity and rarity of HIV-1-infected cells hamper mechanistic interrogations. Here, we used single-cell DOGMA-seq to simultaneously capture transcription factor accessibility, transcriptome, surface proteins, HIV-1 DNA, and HIV-1 RNA in memory CD4+ T cells from six people living with HIV-1 during viremia and after suppressive antiretroviral therapy. We identified increased transcription factor accessibility in latent HIV-1-infected cells (RORC) and transcriptionally active HIV-1-infected cells (interferon regulatory transcription factor [IRF] and activator protein 1 [AP-1])...
October 26, 2023: Immunity
https://read.qxmd.com/read/37920126/skeletal-muscle-dna-methylation-effects-of-exercise-and-hiv
#24
JOURNAL ARTICLE
Catherine M Jankowski, Iain R Konigsberg, Melissa P Wilson, Jing Sun, Todd T Brown, Colleen G Julian, Kristine M Erlandson
Aging, human immunodeficiency virus (HIV) infection, and antiretroviral therapy modify the epigenetic profile and function of cells and tissues, including skeletal muscle (SkM). In some cells, accelerated epigenetic aging begins very soon after the initial HIV infection, potentially setting the stage for the early onset of frailty. Exercise imparts epigenetic modifications in SkM that may underpin some health benefits, including delayed frailty, in people living with HIV (PWH). In this first report of exercise-related changes in SkM DNA methylation among PWH, we investigated the impact of 24 weeks of aerobic and resistance exercise training on SkM (vastus lateralis) DNA methylation profiles and epigenetic age acceleration (EAA) in older, virally suppressed PWH (n = 12) and uninfected controls (n = 18), and associations of EAA with physical function at baseline...
November 3, 2023: Aging Cell
https://read.qxmd.com/read/37886587/epigenetic-aging-in-older-people-living-with-hiv-in-eswatini-a-pilot-study-of-hiv-and-lifestyle-factors-and-epigenetic-aging
#25
Christian K Dye, Haotian Wu, Gabriella L Jackson, Altaye Kidane, Rejoice Nkambule, Nomthandazo G Lukhele, Bongiwe Prudence Malinga, Rhinos Chekenyere, Wafaa M El-Sadr, Andrea A Baccarelli, Tiffany G Harris
BACKGROUND: People living with HIV (PLHIV) on effective antiretroviral therapy (ART) are living near-normal lives. Although they are less susceptible to AIDS-related complications, they remain highly vulnerable to non-communicable diseases (NCD). In this exploratory study of older PLHIV (OPLHIV) in Eswatini, we investigated whether biological aging ( i.e. , the difference between epigenetic age and chronological age, termed 'epigenetic age acceleration [EAA]') was associated with HIV-related parameters, and whether lifestyle factors modified these relationships...
October 5, 2023: Research Square
https://read.qxmd.com/read/37880620/change-of-histone-h3-lysine-14-acetylation-stoichiometry-in-human-monocyte-derived-macrophages-as-determined-by-ms-based-absolute-targeted-quantitative-proteomic-approach-hiv-infection-and-methamphetamine-exposure
#26
JOURNAL ARTICLE
Katarzyna Macur, Andrew Schissel, Fang Yu, Shulei Lei, Brenda Morsey, Howard S Fox, Pawel Ciborowski
BACKGROUND: Histones posttranslational modification represent an epigenetic mechanism that regulate gene expression and other cellular processes. Quantitative mass spectrometry used for the absolute quantification of such modifications provides further insight into cellular responses to extracellular insults such as infections or toxins. Methamphetamine (Meth), a drug of abuse, is affecting the overall function of the immune system. In this report, we developed, validated and applied a targeted, MS-based quantification assay to measure changes in histone H3 lysine 14 acetylation (H3K14Ac) during exposure of human primary macrophages to HIV-1 infection and/or Meth...
October 25, 2023: Clinical Proteomics
https://read.qxmd.com/read/37762667/genomic-factors-and-therapeutic-approaches-in-hiv-associated-neurocognitive-disorders-a-comprehensive-review
#27
REVIEW
Ana Borrajo, Daniel Pérez-Rodríguez, Carlos Fernández-Pereira, José María Prieto-González, Roberto Carlos Agís-Balboa
HIV-associated neurocognitive disorders (HANDs) still persist despite improved life expectancy, reduced viral loads, and decreased infection severity. The number of patients affected by HANDs ranges from (30 to 50) % of HIV-infected individuals. The pathological mechanisms contributing to HANDs and the most serious manifestation of the disease, HIV-associated dementia (HAD), are not yet well understood. Evidence suggests that these mechanisms are likely multifactorial, producing neurocognitive complications involving disorders such as neurogenesis, autophagy, neuroinflammation, and mitochondrial dysfunction...
September 21, 2023: International Journal of Molecular Sciences
https://read.qxmd.com/read/37714998/paired-atac-and-rna-seq-offer-insight-into-the-impact-of-hiv-on-alveolar-macrophages-a-pilot-study
#28
JOURNAL ARTICLE
Bashar S Staitieh, Xin Hu, Samantha M Yeligar, Sara C Auld
People with HIV remain at greater risk for both infectious and non-infectious pulmonary diseases even after antiretroviral therapy initiation and CD4 cell count recovery. These clinical risks reflect persistent HIV-mediated defects in innate and adaptive immunity, including in the alveolar macrophage, a key innate immune effector in the lungs. In this proof-of-concept pilot study, we leveraged paired RNA-seq and ATAC-seq analyses of human alveolar macrophages obtained with research bronchoscopy from people with and without HIV to highlight the potential for recent methodologic advances to generate novel hypotheses about biological pathways that may contribute to impaired pulmonary immune function in people with HIV...
September 15, 2023: Scientific Reports
https://read.qxmd.com/read/37711592/medicinal-chemistry-advances-in-targeting-class-i-histone-deacetylases
#29
REVIEW
Diaaeldin I Abdallah, Elvin D de Araujo, Naman H Patel, Lina S Hasan, Richard Moriggl, Oliver H Krämer, Patrick T Gunning
Histone deacetylases (HDACs) are a class of zinc (Zn)-dependent metalloenzymes that are responsible for epigenetic modifications. HDACs are largely associated with histone proteins that regulate gene expression at the DNA level. This tight regulation is controlled by acetylation [via histone acetyl transferases (HATs)] and deacetylation (via HDACs) of histone and non-histone proteins that alter the coiling state of DNA, thus impacting gene expression as a downstream effect. For the last two decades, HDACs have been studied extensively and indicated in a range of diseases where HDAC dysregulation has been strongly correlated with disease emergence and progression-most prominently, cancer, neurodegenerative diseases, HIV, and inflammatory diseases...
2023: Exploration of targeted anti-tumor therapy
https://read.qxmd.com/read/37701289/the-hiv-2-ogh-double-reporter-virus-shows-that-hiv-2-is-less-cytotoxic-and-less-sensitive-to-reactivation-from-latency-than-hiv-1-in-cell-culture
#30
JOURNAL ARTICLE
Anne Bruggemans, Gerlinde Vansant, Paulien Van de Velde, Zeger Debyser
A better understanding of HIV-1 latency is a research priority in HIV cure research. Conversely, little is known about the latency characteristics of HIV-2, the closely related human lentivirus. Though both viruses cause AIDS, HIV-2 infection progresses more slowly with significantly lower viral loads, even when corrected for CD4+ T cell counts. Hence a direct comparison of latency characteristics between HIV-1 and HIV-2 could provide important clues towards a functional cure. Transduction of SupT1 cells with single-round HIV-1 and HIV-2 viruses with an enhanced green fluorescent protein (eGFP) reporter showed higher levels of eGFP expression for HIV-2 than HIV-1, while HIV-1 expression appeared more cytotoxic...
September 2023: Journal of Virus Eradication
https://read.qxmd.com/read/37675817/cell-type-specific-impact-of-metformin-on-monocyte-epigenetic-age-reversal-in-virally-suppressed-older-people-living-with-hiv
#31
RANDOMIZED CONTROLLED TRIAL
Michael J Corley, Alina P S Pang, Cecilia M Shikuma, Lishomwa C Ndhlovu
The anti-diabetic drug metformin may promote healthy aging. However, few clinical trials of metformin assessing biomarkers of aging have been completed. In this communication, we retrospectively examined the effect of metformin on epigenetic age using principal component (PC)-based epigenetic clocks, mitotic clocks, and pace of aging in peripheral monocytes and CD8+ T cells from participants in two clinical trials of virologically-suppressed people living with HIV (PLWH) with normal glucose receiving metformin...
January 2024: Aging Cell
https://read.qxmd.com/read/37675289/identification-of-the-h3k36me3-reader-ledgf-p75-in-the-pancancer-landscape-and-functional-exploration-in-clear-cell-renal-cell-carcinoma
#32
JOURNAL ARTICLE
Yuwei Zhang, Wei Guo, Yangkun Feng, Longfei Yang, Hao Lin, Pengcheng Zhou, Kejie Zhao, Lin Jiang, Bing Yao, Ninghan Feng
Lens epithelium-derived growth factor (LEDGF/p75) is a reader of epigenetic marks and a potential target for therapeutic intervention. Its involvement in human immunodeficiency virus (HIV) integration and the development of leukemia driven by MLL (also known as KMT2A) gene fusion make it an attractive candidate for drug development. However, exploration of LEDGF/p75 as an epigenetic reader of H3K36me3 in tumors is limited. Here, for the first time, we analyze the role of LEDGF/p75 in multiple cancers via multiple online databases and in vitro experiments...
2023: Computational and Structural Biotechnology Journal
https://read.qxmd.com/read/37661861/epigenetic-signaling-and-crosstalk-in-regulation-of-gene-expression-and-disease-progression
#33
REVIEW
Soumen Manna, Jagdish Mishra, Tirthankar Baral, R Kirtana, Piyasa Nandi, Ankan Roy, Subhajit Chakraborty, Niharika, Samir K Patra
Chromatin modifications - including DNA methylation, modification of histones and recruitment of noncoding RNAs - are essential epigenetic events. Multiple sequential modifications converge into a complex epigenetic landscape. For example, promoter DNA methylation is recognized by MeCP2/methyl CpG binding domain proteins which further recruit SETDB1/SUV39 to attain a higher order chromatin structure by propagation of inactive epigenetic marks like H3K9me3. Many studies with new information on different epigenetic modifications and associated factors are available, but clear maps of interconnected pathways are also emerging...
July 2023: Epigenomics
https://read.qxmd.com/read/37632019/new-concepts-in-therapeutic-manipulation-of-hiv-1-transcription-and-latency-latency-reversal-versus-latency-prevention
#34
REVIEW
Catherine A Lewis, David M Margolis, Edward P Browne
Antiretroviral therapy (ART) has dramatically improved the prognosis for people living with HIV-1, but a cure remains elusive. The largest barrier to a cure is the presence of a long-lived latent reservoir that persists within a heterogenous mix of cell types and anatomical compartments. Efforts to eradicate the latent reservoir have primarily focused on latency reversal strategies. However, new work has demonstrated that the majority of the long-lived latent reservoir is established near the time of ART initiation, suggesting that it may be possible to pair an intervention with ART initiation to prevent the formation of a sizable fraction of the latent reservoir...
July 31, 2023: Viruses
https://read.qxmd.com/read/37625185/study-protocol-using-cohort-data-and-latent-variable-modeling-to-guide-sampling-women-with-type-2-diabetes-and-depressive-symptoms
#35
JOURNAL ARTICLE
Nicole Beaulieu Perez, Gail D'Eramo Melkus, Gary Yu, Janet Brown-Friday, Kathryn Anastos, Brad Aouizerat
BACKGROUND: Depression affects one in three women with Type 2 diabetes, and this concurrence significantly increases the risks of diabetes complications, disability, and early mortality. Depression is underrecognized because of wide variation in presentation and the lack of diagnostic biomarkers. Converging evidence suggests inflammation is a shared biological pathway in diabetes and depression. Overlapping epigenetic associations and social determinants of diabetes and depression implicate inflammatory pathways as a common thread...
September 2023: Nursing Research
https://read.qxmd.com/read/37606452/association-of-toll-like-receptor-gene-polymorphisms-with-tuberculosis-in-hiv-positive-participants
#36
JOURNAL ARTICLE
Svetlana Salamaikina, Vitaly Korchagin, Ekaterina Kulabukhova, Konstantin Mironov, Vera Zimina, Alexey Kravtchenko, Vasily Akimkin
Genetic factors in the HIV-background may play a significant role in the susceptibility to secondary diseases, like tuberculosis, which is the leading cause in mortality of HIV-positive people. Toll-like receptors (TLRs) are considered to be receptors for adaptive immunity, and polymorphisms in TLR genes can influence the activity of the immune response to infection. We conducted a case-control study of the association of TLR gene polymorphisms with the risk of tuberculosis coinfection in a multi-country sample of HIV-positive participants...
July 25, 2023: Epigenomes
https://read.qxmd.com/read/37578230/a-high-throughput-screening-assay-for-silencing-established-hiv-1-macrophage-infection-identifies-nucleoside-analogs-that-perturb-h3k9me3-on-proviral-genomes
#37
JOURNAL ARTICLE
Yanjie Yi, Urvi Zankharia, Joel A Cassel, Fang Lu, Joseph M Salvino, Paul M Lieberman, Ronald G Collman
HIV-infected macrophages are long-lived cells that represent a barrier to functional cure. Additionally, low-level viral expression by central nervous system (CNS) macrophages contributes to neurocognitive deficits that develop despite antiretroviral therapy (ART). We recently identified H3K9me3 as an atypical epigenetic mark associated with chronic HIV infection in macrophages. Thus, strategies are needed to suppress HIV-1 expression in macrophages, but the unique myeloid environment and the responsible macrophage/CNS-tropic strains require cell/strain-specific approaches...
August 14, 2023: Journal of Virology
https://read.qxmd.com/read/37554468/nanotechnology-prospects-in-brain-therapeutics-concerning-gene-targeting-and-nose-to-brain-administration
#38
REVIEW
Dong-Dong Wu, Yasmine Ahmed Salah, Ebenezeri Erasto Ngowi, Yan-Xia Zhang, Saadullah Khattak, Nazeer Hussain Khan, Yan Wang, Tao Li, Zi-Hua Guo, Yan-Mei Wang, Xin-Ying Ji
Neurological diseases are one of the most pressing issues in modern times worldwide. It thus possesses explicit attention from researchers and medical health providers to guard public health against such an expanding threat. Various treatment modalities have been developed in a remarkably short time but, unfortunately, have yet to lead to the wished-for efficacy or the sought-after clinical improvement. The main hurdle in delivering therapeutics to the brain has always been the blood-brain barrier which still represents an elusive area with lots of mysteries yet to be solved...
August 18, 2023: IScience
https://read.qxmd.com/read/37535041/hiv-1-transcriptional-modulation-novel-host-factors-and-prospective-therapeutic-strategies
#39
REVIEW
Quentin M R Gibaut, Luisa P Mori, Susana T Valente
PURPOSE OF REVIEW: This review highlights advances in HIV transcription and epigenetic latency mechanisms and outlines current therapeutic approaches to eliminate or block the HIV-1 latent reservoir. RECENT FINDINGS: Novel host factors have been reported to modulate HIV-1 transcription and latency. Chromatin affinity purification strategies followed by mass spectrometry (ChAP-MS) identified the chaperone protein p32 to play an important role in HIV-1 transcriptional regulation via interactions with the viral transcriptional activator Tat...
September 1, 2023: Current Opinion in HIV and AIDS
https://read.qxmd.com/read/37535039/single-cell-multiomic-understanding-of-hiv-1-reservoir-at-epigenetic-transcriptional-and-protein-levels
#40
JOURNAL ARTICLE
Michelle Wong, Yulong Wei, Ya-Chi Ho
PURPOSE OF REVIEW: The success of HIV-1 eradication strategies relies on in-depth understanding of HIV-1-infected cells. However, HIV-1-infected cells are extremely heterogeneous and rare. Single-cell multiomic approaches resolve the heterogeneity and rarity of HIV-1-infected cells. RECENT FINDINGS: Advancement in single-cell multiomic approaches enabled HIV-1 reservoir profiling across the epigenetic (ATAC-seq), transcriptional (RNA-seq), and protein levels (CITE-seq)...
September 1, 2023: Current Opinion in HIV and AIDS
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