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https://www.readbyqxmd.com/read/28539614/the-ccr5-antagonist-maraviroc-reverses-hiv-1-latency-in-vitro-alone-or-in-combination-with-the-pkc-agonist-bryostatin-1
#1
María Rosa López-Huertas, Laura Jiménez-Tormo, Nadia Madrid-Elena, Carolina Gutiérrez, Sara Rodríguez-Mora, Mayte Coiras, José Alcamí, Santiago Moreno
A potential strategy to cure HIV-1 infection is to use latency reversing agents (LRAs) to eliminate latent reservoirs established in resting CD4+ T (rCD4+) cells. As no drug has been shown to be completely effective, finding new drugs and combinations are of increasing importance. We studied the effect of Maraviroc (MVC), a CCR5 antagonist that activates NF-κB, on HIV-1 replication from latency. HIV-1-latency models based on CCL19 or IL7 treatment, before HIV-1 infection were used. Latently infected primary rCD4+ or central memory T cells were stimulated with MVC alone or in combination with Bryostatin-1, a PKC agonist known to reverse HIV-1 latency...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28539449/anti-hiv-1-adcc-antibodies-following-latency-reversal-and-treatment-interruption
#2
Wen Shi Lee, Anne B Kristensen, Thomas A Rasmussen, Martin Tolstrup, Lars Østergaard, Ole S Søgaard, Bruce D Wines, P Mark Hogarth, Arnold Reynaldi, Miles P Davenport, Sean Emery, Janaki Amin, David A Cooper, Virginia L Kan, Julie Fox, Henning Gruell, Matthew S Parsons, Stephen J Kent
There is growing interest in utilizing antibody-dependent cellular cytotoxicity (ADCC) to eliminate infected cells following reactivation from HIV-1 latency. A potential barrier is that HIV-1-specific ADCC antibodies decline in patients on long-term antiretroviral therapy (ART) and may not be sufficient to eliminate reactivated latently infected cells. It is not known whether reactivation from latency with latency-reversing agents (LRA) could provide sufficient antigenic stimulus to boost HIV-1-specific ADCC...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28537062/evaluation-of-the-immunogenicity-and-impact-on-the-latent-hiv-1-reservoir-of-a-conserved-region-vaccine-mva-hivconsv-in-antiretroviral-therapy-treated-subjects
#3
REVIEW
Gemma Hancock, Sara Morón-López, Jakub Kopycinski, Maria C Puertas, Eleni Giannoulatou, Annie Rose, Maria Salgado, Emma-Jo Hayton, Alison Crook, Catharine Morgan, Brian Angus, Fabian Chen, Hongbing Yang, Javier Martinez-Picado, Tomas Hanke, Lucy Dorrell
INTRODUCTION: Vaccines may be key components of a curative strategy for HIV-1. We investigated whether a novel immunogen, HIVconsv, designed to re-direct T cell responses to conserved viral epitopes, could impact the HIV-1 reservoir in chronic antiretroviral therapy (ART)-treated subjects when delivered by modified vaccinia virus Ankara (MVA). METHODS: Nineteen virologically suppressed individuals were randomized to receive vaccinations with MVA.HIVconsv (5.5 × 10(7) plaque-forming units, pfu, n = 8; 2...
May 19, 2017: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/28536264/exosomes-from-uninfected-cells-activate-transcription-of-latent-hiv-1
#4
Robert A Barclay, Angela Schwab, Catherine DeMarino, Yao Akpamagbo, Benjamin Lepene, Seble Kassaye, Sergey Iordanskiy, Fatah Kashanchi
HIV-1 infection causes AIDS, infecting millions worldwide. The virus can persist in a state of chronic infection due to its ability to become latent. We have previously shown a link between HIV-1 infection and exosome production. Specifically, we have reported that exosomes transport viral proteins and RNA from infected cells to neighboring uninfected cells. These viral products could then elicit an innate immune response, leading to activation of the Toll-like receptor (TLR) and NF-κB pathways. In this study, we asked whether exosomes from uninfected cells could activate latent HIV-1 in infected cells...
May 23, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28534887/when-is-early-antiretroviral-therapy-early-enough-for-hiv-remission
#5
Eva Poveda, Manuelo Cresp
Several strategies to reduce and control the HIV reservoir are being evaluating to achieve the great challenge of HIV remission or functional cure. Some of these are based on immune and gene therapy, or in the use of agents with latency reversing properties. Moreover, acute HIV infection and the impact of early antiretroviral treatment (ART) initiation is another key issue of current research. It has been demonstrated that ART initiation during acute HIV infection minimizes the establishment of the latent HIV reservoir...
May 23, 2017: AIDS Reviews
https://www.readbyqxmd.com/read/28529952/advancements-in-developing-strategies-for-sterilizing-and-functional-hiv-cures
#6
REVIEW
Wei Xu, Haoyang Li, Qian Wang, Chen Hua, Hanzhen Zhang, Weihua Li, Shibo Jiang, Lu Lu
Combined antiretroviral therapy (cART) has been successful in prolonging lifespan and reducing mortality of patients infected with human immunodeficiency virus (HIV). However, the eradication of latent HIV reservoirs remains a challenge for curing HIV infection (HIV cure) because of HIV latency in primary memory CD4(+) T cells. Currently, two types of HIV cures are in development: a "sterilizing cure" and a "functional cure." A sterilizing cure refers to the complete elimination of replication-competent proviruses in the body, while a functional cure refers to the long-term control of HIV replication without treatment...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28529033/high-throughput-characterization-of-hiv-1-reservoir-reactivation-using-a-single-cell-in-droplet-pcr-assay
#7
Robert W Yucha, Kristen S Hobbs, Emily Hanhauser, Louise E Hogan, Wildaliz Nieves, Mehmet O Ozen, Fatih Inci, Vanessa York, Erica A Gibson, Cassandra Thanh, Hadi Shafiee, Rami El Assal, Maja Kiselinova, Yvonne P Robles, Helen Bae, Kaitlyn S Leadabrand, ShuQi Wang, Steven G Deeks, Daniel R Kuritzkes, Utkan Demirci, Timothy J Henrich
Reactivation of latent viral reservoirs is on the forefront of HIV-1 eradication research. However, it is unknown if latency reversing agents (LRAs) increase the level of viral transcription from cells producing HIV RNA or harboring transcriptionally-inactive (latent) infection. We therefore developed a microfluidic single-cell-in-droplet (scd)PCR assay to directly measure the number of CD4(+) T cells that produce unspliced (us)RNA and multiply spliced (ms)RNA following ex vivo latency reversal with either an histone deacetylase inhibitor (romidepsin) or T cell receptor (TCR) stimulation...
May 4, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28520970/perspectives-on-human-immunodeficiency-virus-hiv-cure-hiv-persistence-in-tissue
#8
Eli A Boritz, Daniel C Douek
The uneven anatomic distribution of cell subsets that harbor human immunodeficiency virus (HIV) during antiretroviral therapy (ART) complicates investigation of the barriers to HIV cure. Here we propose that while previous studies done largely in blood cells have led to important investigations into HIV latency, other important mechanisms of HIV persistence during ART may not be readily apparent in the bloodstream. We specifically consider as an example the question of ongoing HIV replication during ART. We discuss how growing understanding of key anatomic sanctuaries for the virus can inform future experiments aimed at further clarifying this issue...
March 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28520964/proviral-latency-persistent-human-immunodeficiency-virus-infection-and-the-development-of-latency-reversing-agents
#9
David M Margolis, Nancie M Archin
Quiescent proviral genomes that persist during human immunodeficiency virus type 1 (HIV-1) infection despite effective antiretroviral therapy (ART) can fuel rebound viremia after ART interruption and is a central obstacle to the cure of HIV infection. The induction of quiescent provirus is the goal of a new class of potential therapeutics, latency reversing agents (LRAs). The discovery, development, and testing of HIV LRAs is a key part of current efforts to develop latency reversal and viral clearance strategies to eradicate established HIV infection...
March 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28512685/modeling-brain-lentiviral-infections-during-antiretroviral-therapy-in-aids
#10
Weston C Roda, Michael Y Li, Michael S Akinwumi, Eugene L Asahchop, Benjamin B Gelman, Kenneth W Witwer, Christopher Power
Understanding HIV-1 replication and latency in different reservoirs is an ongoing challenge in the care of patients with HIV/AIDS. A mathematical model was created to describe and predict the viral dynamics of HIV-1 and SIV infection within the brain during effective combination antiretroviral therapy (cART). The mathematical model was formulated based on the biology of lentiviral infection of brain macrophages and used to describe the dynamics of transmission and progression of lentiviral infection in brain...
May 16, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28511815/signature-of-the-sleeper-cell-a-biomarker-of-hiv-latency-revealed
#11
Satish K Pillai, Steven G Deeks
HIV establishes a reservoir in latently infected T cells, and this reservoir has long hampered curative approaches. A recent study by Descours et al. identifies CD32a as a marker of latently infected T cells, potentially opening the way to the development of strategies that directly target this critical HIV reservoir.
May 13, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28494238/smyd2-mediated-histone-methylation-contributes-to-hiv-1-latency
#12
Daniela Boehm, Mark Jeng, Gregory Camus, Andrea Gramatica, Roland Schwarzer, Jeffrey R Johnson, Philip A Hull, Mauricio Montano, Naoki Sakane, Sara Pagans, Robert Godin, Steven G Deeks, Nevan J Krogan, Warner C Greene, Melanie Ott
Transcriptional latency of HIV is a last barrier to viral eradication. Chromatin-remodeling complexes and post-translational histone modifications likely play key roles in HIV-1 reactivation, but the underlying mechanisms are incompletely understood. We performed an RNAi-based screen of human lysine methyltransferases and identified the SET and MYND domain-containing protein 2 (SMYD2) as an enzyme that regulates HIV-1 latency. Knockdown of SMYD2 or its pharmacological inhibition reactivated latent HIV-1 in T cell lines and in primary CD4(+) T cells...
May 10, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28494231/hiv-latency-gets-a-new-histone-mark
#13
Bryan C Nikolai, Qin Feng
Transcriptional latency of integrated HIV-1 provirus represents a major obstacle to curing HIV. In this issue of Cell Host & Microbe, Boehm et al. (2017) identify a new lysine methyltransferase that writes a repressive histone mark associated with HIV-1 latency. The results are important for strategies to pharmacologically reverse HIV-1 latency.
May 10, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28484438/the-role-of-hcmv-and-hiv-1-micrornas-processing-and-mechanisms-of-action-during-viral-infection
#14
REVIEW
Doriana Fruci, Rossella Rota, Angela Gallo
Viruses infect host cells releasing their genome (DNA or RNA) containing all information needed to replicate themselves. The viral genome takes control of the cells and helps the virus to evade the host immune system. Some viruses alter the functions of infected cells without killing them. In some cases infected cells lose control over normal cell proliferation and becomes cancerous. Viruses, such as HCMV and HIV-1, may leave their viral genome in the host cells for a certain period (latency) and begin to replicate when the cells are stressed causing diseases...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28476627/-the-impact-of-mycobacterium-tuberculosis-immune-evasion-on-protective-immunity-implications-for-tb-vaccine-design-meeting-report
#15
Cesar Boggiano, Katrin Eichelberg, Lakshmi Ramachandra, Jaqueline Shea, Lalita Ramakrishnan, Samuel Behar, Joel D Ernst, Steven A Porcelli, Markus Maeurer, Hardy Kornfeld
Tuberculosis (TB) is the major cause of death from infectious diseases around the world, particularly in HIV infected individuals. TB vaccine design and development have been focused on improving Bacille Calmette-Guérin (BCG) and evaluating recombinant and viral vector expressed Mycobacterium tuberculosis (Mtb) proteins, for boosting BCG-primed immunity, but these approaches have not yet yielded significant improvements over the modest effects of BCG in protecting against infection or disease. On March 7-8, 2016, the National Institute of Allergy and Infectious Diseases (NIAID) convened a workshop on "The Impact of Mtb Immune Evasion on Protective Immunity: Implications for TB Vaccine Design" with the goal of defining immune mechanisms that could be targeted through novel research approaches, to inform vaccine design and immune therapeutic interventions for prevention of TB...
May 2, 2017: Vaccine
https://www.readbyqxmd.com/read/28473642/selective-vulnerability-of-striatal-d2-versus-d1-dopamine-receptor-expressing-medium-spiny-neurons-in-hiv-1-tat-transgenic-male-mice
#16
Christina J Schier, William D Marks, Jason J Paris, Aaron J Barbour, Virginia D McLane, William F Maragos, A Rory McQuiston, Pamela E Knapp, Kurt F Hauser
Despite marked regional differences in HIV susceptibility within the CNS, there has been surprisingly little exploration into the differential vulnerability among neuron types and the circuits they underlie. The dorsal striatum is especially susceptible, harboring high viral loads and displaying marked neuropathology-with motor impairment a frequent manifestation of chronic infection; yet, little is known about the response of individual striatal neuron types to HIV or how this disrupts function. Consequently, we examined the morphological, electrophysiological, and anxiety-like and exploratory/locomotor behavioral effects of HIV-1 Tat in dopamine subtype 1 (D1) and dopamine subtype 2 (D2) receptor-expressing striatal medium spiny neurons (MSNs) by breeding transgenic Tat-expressing mice to Drd1a-tdTomato- or Drd2-eGFP- reporter mice...
May 4, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28472156/genetically-barcoded-siv-facilitates-enumeration-of-rebound-variants-and-estimation-of-reactivation-rates-in-nonhuman-primates-following-interruption-of-suppressive-antiretroviral-therapy
#17
Christine M Fennessey, Mykola Pinkevych, Taina T Immonen, Arnold Reynaldi, Vanessa Venturi, Priyanka Nadella, Carolyn Reid, Laura Newman, Leslie Lipkey, Kelli Oswald, William J Bosche, Matthew T Trivett, Claes Ohlen, David E Ott, Jacob D Estes, Gregory Q Del Prete, Jeffrey D Lifson, Miles P Davenport, Brandon F Keele
HIV and SIV infection dynamics are commonly investigated by measuring plasma viral loads. However, this total viral load value represents the sum of many individual infection events, which are difficult to independently track using conventional sequencing approaches. To overcome this challenge, we generated a genetically tagged virus stock (SIVmac239M) with a 34-base genetic barcode inserted between the vpx and vpr accessory genes of the infectious molecular clone SIVmac239. Next-generation sequencing of the virus stock identified at least 9,336 individual barcodes, or clonotypes, with an average genetic distance of 7 bases between any two barcodes...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28471170/resveratrol-reactivates-latent-hiv-through-increasing-histone-acetylation-and-activating-heat-shock-factor-1
#18
Xiaoyun Zeng, Xiaoyan Pan, Xinfeng Xu, Jian Lin, Fuchang Que, Yuanxin Tian, Lin Li, Shuwen Liu
The persistence of latent HIV reservoirs presents a significant challenge to viral eradication. Effective latency reversing agents (LRAs) based on "shock and kill" strategy are urgently needed. The natural phytoalexin resveratrol has been demonstrated to enhance HIV gene expression, although its mechanism remains unclear. In this study, we demonstrated that resveratrol was able to reactivate latent HIV without global T cell activation in vitro. Mode of action studies showed resveratrol-mediated reactivation from latency did not involve the activation of silent mating type information regulation 2 homologue 1 (SIRT1), which belonged to class-3 histone deacetylase (HDAC)...
May 23, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28467486/the-effect-of-ingenol-b-on-the-suppressive-capacity-of-elite-suppressor-hiv-specific-cd8-t-cells
#19
Abena K Kwaa, Kennedy Goldsborough, Victoria E Walker-Sperling, Luiz F Pianowski, Lucio Gama, Joel N Blankson
BACKGROUND: Some latency-reversing agents (LRAs) inhibit HIV-specific CD8+ T cell responses. In a prior study of protein kinase C (PKC) agonists, we found that bryostatin-1 inhibited elite controller/suppressor (ES) CD8+ T cell suppressive activity whereas prostratin had no effect. Ingenol-B is another PKC agonist with potent LRA activity both by itself and in combination with the bromodomain inhibitor JQ1; however its effect on CD8+ T cell mediated control of HIV-1 replication is unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28465838/a-critical-review-of-the-evidence-concerning-the-hiv-latency-reversing-effect-of-disulfiram-the-possible-explanations-for-its-inability-to-reduce-the-size-of-the-latent-reservoir-in-vivo-and-the-caveats-associated-with-its-use-in-practice
#20
REVIEW
Harry D J Knights
Combination antiretroviral therapy (cART) effectively suppresses the replication of human immunodeficiency virus type 1 (HIV-1), improves immune function, and decreases the morbidity of acquired immune deficiency syndrome (AIDS). However, it is unable to eradicate the virus because it does not eliminate latently infected cells. The latent reservoir poses the major barrier to an HIV-1 cure. The "shock and kill" strategy aims to reactivate the virus and destroy latently infected cells. Many latency reversing agents (LRAs) reactivate HIV in vitro, but the absence of damaging side-effects and efficacy in vivo make disulfiram particularly promising...
2017: AIDS Research and Treatment
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