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Hiv latency

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https://www.readbyqxmd.com/read/28107222/romidepsin-induced-hiv-1-viremia-during-effective-art-contains-identical-viral-sequences-with-few-deleterious-mutations
#1
Anni Winckelmann, Kirston Barton, Bonnie Hiener, Timothy E Schlub, Wei Shao, Thomas A Rasmussen, Lars Østergaard, Ole S Søgaard, Martin Tolstrup, Sarah Palmer
OBJECTIVE: To investigate the origin of the HIV-1 viremia induced by the latency-reversing agent romidepsin. DESIGN: Six individuals on suppressive antiretroviral therapy received romidepsin administered intravenously once weekly for three consecutive weeks. CD4+ T-cells were obtained at baseline, following the second and third romidepsin infusion, and 10 weeks after the final romidepsin treatment. METHODS: Single-genome sequencing of the env region was used to genetically characterize the virus from proviral DNA, the transcribed cell-associated RNA and the plasma RNA pool...
January 19, 2017: AIDS
https://www.readbyqxmd.com/read/28095796/a-severe-case-of-visceral-leishmaniasis-and-liposomal-amphotericin-b-treatment-failure-in-an-immunosuppressed-patient-15%C3%A2-years-after-exposure
#2
Anna Eichenberger, Annina E Buechi, Andreas Neumayr, Chistroph Hatz, Andri Rauch, Marc Huguenot, Eva Diamantis-Karamitopoulou, Cornelia Staehelin
BACKGROUND: Visceral leishmaniasis (VL) is a protozoan disease, which is responsible for 200.000-400.000 yearly infections worldwide. If left untreated, the fatality rate can be as high as 100% within 2 years. 90% of cases occur in just six countries: India, Bangladesh, Sudan, South Sudan, Ethiopia and Brazil. It is thus a disease rarely seen by physicians in Europe or North America. We report on the fatal case of VL in an 80-year-old immunosuppressed patient who presented with a latency of over 15 years after having visited an endemic region...
January 17, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28094770/rapamycin-mediated-mtor-inhibition-uncouples-hiv-1-latency-reversal-from-cytokine-associated-toxicity
#3
Alyssa R Martin, Ross A Pollack, Adam Capoferri, Richard F Ambinder, Christine M Durand, Robert F Siliciano
Current strategies for HIV-1 eradication require the reactivation of latent HIV-1 in resting CD4+ T cells (rCD4s). Global T cell activation is a well-characterized means of inducing HIV-1 transcription, but is considered too toxic for clinical applications. Here, we have explored a strategy that involves a combination of immune activation and the immunosuppressive mTOR inhibitor rapamycin. In purified rCD4s from HIV-1-infected individuals on antiretroviral therapy, rapamycin treatment downregulated markers of toxicity, including proinflammatory cytokine release and cellular proliferation that were induced after potent T cell activation using αCD3/αCD28 antibodies...
January 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28091416/factors-associated-with-the-size-of-hiv-dna-reservoir
#4
REVIEW
Ni-Dan Wang, Tai-Sheng Li
OBJECTIVE: To review the recent literatures related to the factors associated with the size of the HIV reservoir and their clinical significance. DATA SOURCES: Literatures related to the size of HIV DNA was collected from PubMed published from 1999 to June 2016. STUDY SELECTION: All relevant articles on the HIV DNA and reservoir were collected and reviewed, with no limitation of study design. RESULTS: The composition and development of the HIV-1 DNA reservoir in either treated or untreated patients is determined by integrated mechanism comprising viral characteristics, immune system, and treatment strategies...
2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28086908/hiv-integration-sites-in-latently-infected-cell-lines-evidence-of-ongoing-replication
#5
Jori Symons, Abha Chopra, Eva Malantinkova, Ward De Spiegelaere, Shay Leary, Don Cooper, Chike O Abana, Ajantha Rhodes, Simin D Rezaei, Linos Vandekerckhove, Simon Mallal, Sharon R Lewin, Paul U Cameron
BACKGROUND: Assessing the location and frequency of HIV integration sites in latently infected cells can potentially inform our understanding of how HIV persists during combination antiretroviral therapy. We developed a novel high throughput sequencing method to evaluate HIV integration sites in latently infected cell lines to determine whether there was virus replication or clonal expansion in these cell lines observed as multiple integration events at the same position. RESULTS: We modified a previously reported method using random DNA shearing and PCR to allow for high throughput robotic processing to identify the site and frequency of HIV integration in latently infected cell lines...
January 13, 2017: Retrovirology
https://www.readbyqxmd.com/read/28077644/ultrasensitive-hiv-1-p24-detects-single-infected-cells-and-differences-in-reservoir-induction-by-latency-reversal-agents
#6
Caroline Pereira Bittencourt Passaes, Timothée Bruel, Jérémie Decalf, Annie David, Mathieu Angin, Valerie Monceaux, Michaela Muller-Trutwin, Nicolas Noel, Katia Bourdic, Olivier Lambotte, Matthew L Albert, Darragh Duffy, Olivier Schwartz, Asier Sáez-Cirión
: The existence of HIV reservoirs in infected individuals under cART represents a major obstacle towards cure. Viral reservoirs are assessed by quantification of HIV nucleic acids, which does not discriminate between infectious and defective viruses, or by viral outgrowth assays, which requires large number of cells and long-term cultures. Here, we used an ultrasensitive p24 digital assay, which we report to be 1000 fold more sensitive than classical ELISA in the quantification of HIV-1 Gag p24 production in HIV-infected individuals samples...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28074347/pattern-and-motion-related-visual-evoked-potentials-in-hiv-infected-adults
#7
Jana Szanyi, Jan Kremlacek, Zuzana Kubova, Miroslav Kuba, Pavel Gebousky, Jaroslav Kapla, Juraj Szanyi, Frantisek Vit, Jana Langrova
PURPOSE: The goal of the current study was to explore visual function in virally suppressed HIV patients undergoing combined antiretroviral therapy (cART) by using pattern-reversal and motion-onset visual evoked potentials (VEPs). METHODS: The pattern-reversal and motion-onset VEPs were recorded in 20 adult HIV+ patients with a mean age of 38 years and CD4 cell counts ≥230 × 10(6) cells/L of blood. RESULTS: Nine out of 20 patients displayed VEP abnormalities...
January 10, 2017: Documenta Ophthalmologica. Advances in Ophthalmology
https://www.readbyqxmd.com/read/28073694/hiv-latency-should-we-shock-or-lock
#8
REVIEW
Gilles Darcis, Benoit Van Driessche, Carine Van Lint
Combinatory antiretroviral therapy (cART) increases the survival and quality of life of HIV-1-infected patients. However, interruption of therapy almost invariably leads to the re-emergence of detectable viral replication because HIV-1 persists in viral latent reservoirs. Improved understanding of the molecular mechanisms involved in HIV-1 latency has paved the way for innovative strategies that attempt to purge latent virus. In this article we discuss the results of the broadly explored 'shock and kill' strategy, and also highlight the major hurdles facing this approach...
January 7, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28069134/the-multifaceted-contributions-of-chromatin-to-hiv-1-integration-transcription-and-latency
#9
E De Crignis, T Mahmoudi
The capacity of the human immunodeficiency virus (HIV-1) to establish latent infections constitutes a major barrier to the development of a cure for HIV-1. In latent infection, replication competent HIV-1 provirus is integrated within the host genome but remains silent, masking the infected cells from the activity of the host immune response. Despite the progress in elucidating the molecular players that regulate HIV-1 gene expression, the mechanisms driving the establishment and maintenance of latency are still not fully understood...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28064549/mother-to-child-transmission-of-human-immunodeficiency-virus-hiv-among-hiv-infected-pregnant-women-on-highly-active-anti-retroviral-therapy-with-premature-rupture-of-membranes-at-term
#10
George Uchenna Eleje, Emeka Stephen Edokwe, Joseph Ifeanyichukwu Ikechebelu, Chinyere Ukamaka Onubogu, Ebele Francesca Ugochukwu, Princeston Chukwuemeka Okam, Adaobi Maryann Ibekwe
PURPOSE: To determine mother-to-child transmission (MTCT) rate and associated risk factors of human immune-deficiency virus (HIV) among HIV-infected pregnant women with term premature rupture of membranes (PROM) in comparison with those without PROM at term. MATERIALS AND METHODS: All optimally managed HIV-positive pregnant women of Nnamdi Azikiwe University Teaching Hospital, on highly active anti-retroviral therapy (HAART) who had PROM at term were enrolled. Maternal HIV-1 viral load was not assessed...
January 8, 2017: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/27998285/are-t-cells-the-only-hiv-1-reservoir
#11
REVIEW
Abraham Joseph Kandathil, Sho Sugawara, Ashwin Balagopal
Current antiretroviral therapies have improved the duration and quality of life of people living with HIV-1. However, viral reservoirs impede complete eradication of the virus. Although there are many strategies to eliminate infectious virus, the most actively pursued are latency reversing agents in conjunction with immune modulation. This strategy, known as "shock and kill", has been tested primarily against the most widely recognized HIV-1 latent reservoir found in resting memory CD4+ T cells. This is in part because of the dearth of conclusive evidence about the existence of non-T cell reservoirs...
December 20, 2016: Retrovirology
https://www.readbyqxmd.com/read/27998278/janus-kinase-inhibition-suppresses-pkc-induced-cytokine-release-without-affecting-hiv-1-latency-reversal-ex-vivo
#12
Adam M Spivak, Erin T Larragoite, McKenna L Coletti, Amanda B Macedo, Laura J Martins, Alberto Bosque, Vicente Planelles
BACKGROUND: Despite the durable viral suppression afforded by antiretroviral therapy, HIV-1 eradication will require strategies to target latently infected cells that persist in infected individuals. Protein kinase C (PKC) activation is a promising strategy to reactivate latent proviruses and allow for subsequent recognition and clearance of infected cells by the immune system. Ingenol derivatives are PKC agonists that induce latency reversal but also lead to T cell activation and the release of pro-inflammatory cytokines, which would be undesirable in vivo...
December 20, 2016: Retrovirology
https://www.readbyqxmd.com/read/27994072/hiv-1-latency-reversing-agents-prostratin-and-bryostatin-1-induce-blood-brain-barrier-disruption-inflammation-and-modulate-leukocyte-adhesion-transmigration
#13
Clélia Dental, Alizé Proust, Michel Ouellet, Corinne Barat, Michel J Tremblay
A shock-and-kill approach involving the simultaneous treatment of HIV-1-infected patients with latency-reversing agents (LRAs) and combination antiretroviral therapy was proposed as a means to eradicate viral reservoirs. Currently available LRAs cannot discriminate between HIV-1-infected and uninfected cells. Therefore, the risks and benefits of using broad-spectrum LRAs need to be carefully evaluated, particularly in the CNS, where inflammation and leukocyte transmigration must be tightly regulated. We used a real-time impedance-sensing system to dynamically record the impact of different classes of LRAs on the integrity of tight monolayers of the immortalized human cerebral microvascular endothelial cell line hCMEC/D3...
December 19, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27993846/nonnucleoside-reverse-transcriptase-inhibitors-reduce-hiv-1-virus-production-from-latently-infected-resting-cd4-t-cells-following-latency-reversal
#14
Jennifer M Zerbato, Gilda Tachedjian, Nicolas Sluis-Cremer
Therapeutic strategies that target the latent HIV-1 reservoir in resting CD4+ T cells of infected-individuals are always administered in the presence of combination antiretroviral therapy. Using a primary cell of HIV-1 latency, we evaluated whether different antiviral drug classes affected latency reversal (as assessed by extracellular virus production) by anti-CD3/CD28 monoclonal antibodies or by bryostatin 1. We found that the nonnucleoside reverse transcriptase inhibitors efavirenz and rilpivirine significantly decreased HIV-1 production by ≥ 1 log...
December 19, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27990142/homeostatically-maintained-resting-naive-cd4-t-cells-resist-latent-hiv-reactivation
#15
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
https://www.readbyqxmd.com/read/27978436/the-mtor-complex-controls-hiv-latency
#16
Emilie Besnard, Shweta Hakre, Martin Kampmann, Hyung W Lim, Nina N Hosmane, Alyssa Martin, Michael C Bassik, Erik Verschueren, Emilie Battivelli, Jonathan Chan, J Peter Svensson, Andrea Gramatica, Ryan J Conrad, Melanie Ott, Warner C Greene, Nevan J Krogan, Robert F Siliciano, Jonathan S Weissman, Eric Verdin
A population of CD4 T lymphocytes harboring latent HIV genomes can persist in patients on antiretroviral therapy, posing a barrier to HIV eradication. To examine cellular complexes controlling HIV latency, we conducted a genome-wide screen with a pooled ultracomplex shRNA library and in vitro system modeling HIV latency and identified the mTOR complex as a modulator of HIV latency. Knockdown of mTOR complex subunits or pharmacological inhibition of mTOR activity suppresses reversal of latency in various HIV-1 latency models and HIV-infected patient cells...
December 14, 2016: Cell Host & Microbe
https://www.readbyqxmd.com/read/27978431/hiv-latency-torn-down
#17
Mauro Giacca
Combination therapy for HIV infection is effective at controlling disease but fails to eradicate the virus because a persistent reservoir of cells harbors latent HIV DNA. In this issue of Cell Host & Microbe, Besnard et al. (2016) show that the mTOR kinase is essential to reactivate HIV from latency.
December 14, 2016: Cell Host & Microbe
https://www.readbyqxmd.com/read/27941949/in-vitro-effects-of-the-small-molecule-protein-kinase-c-agonists-on-hiv-latency-reactivation
#18
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/27928016/promising-role-of-toll-like-receptor-8-agonist-in-concert-with-prostratin-for-activation-of-silent-hiv
#19
M A Rochat, E Schlaepfer, R F Speck
: The persistence of latently HIV-infected cells in patients under combined anti-retroviral treatment (cART) remains the major hurdle for HIV eradication. Thus far, individual compounds have not been sufficiently potent to reactivate latent virus and guarantee its elimination in vivo Thus, we hypothesized that transcriptional enhancers, in concert with compounds triggering the innate immune system, are more efficient in reversing latency by creating a Th1 supportive milieu that acts against latently HIV-infected cells at various levels...
December 7, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27910923/protein-expression-from-unintegrated-hiv-1-dna-introduces-bias-in-primary-in-vitro-post-integration-latency-models
#20
Pawel Bonczkowski, Marie-Angélique De Scheerder, Eva Malatinkova, Alexandra Borch, Zora Melkova, Renate Koenig, Ward De Spiegelaere, Linos Vandekerckhove
To understand the persistence of latently HIV-1 infected cells in virally suppressed infected patients, a number of in vitro models of HIV latency have been developed. In an attempt to mimic the in vivo situation as closely as possible, several models use primary cells and replication-competent viruses in combination with antiretroviral compounds to prevent ongoing replication. Latency is subsequently measured by HIV RNA and/or protein production after cellular activation. To discriminate between pre- and post-integration latency, integrase inhibitors are routinely used, preventing novel integrations upon cellular activation...
December 2, 2016: Scientific Reports
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