keyword
MENU ▼
Read by QxMD icon Read
search

Latent hiv reservoir

keyword
https://www.readbyqxmd.com/read/28073694/hiv-latency-should-we-shock-or-lock
#1
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/27998285/are-t-cells-the-only-hiv-1-reservoir
#2
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/27993846/nonnucleoside-reverse-transcriptase-inhibitors-reduce-hiv-1-virus-production-from-latently-infected-resting-cd4-t-cells-following-latency-reversal
#3
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
#4
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/27978431/hiv-latency-torn-down
#5
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/27974196/a-combinatorial-crispr-cas9-attack-on-hiv-1-dna-extinguishes-all-infectious-provirus-in-infected-t-cell-cultures
#6
Gang Wang, Na Zhao, Ben Berkhout, Atze T Das
Current drug therapies effectively suppress HIV-1 replication but do not inactivate the provirus that persists in latent reservoirs. Recent studies have found that the guide RNA (gRNA)-directed CRISPR/Cas9 system can be used for sequence-specific attack on this proviral DNA. Although potent inhibition of virus replication was reported, HIV-1 can escape from a single antiviral gRNA by mutation of the target sequence. Here, we demonstrate that combinations of two antiviral gRNAs delay viral escape, and identify two gRNA combinations that durably block virus replication...
December 13, 2016: Cell Reports
https://www.readbyqxmd.com/read/27941949/in-vitro-effects-of-the-small-molecule-protein-kinase-c-agonists-on-hiv-latency-reactivation
#7
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/27941817/nuclear-landscape-of-hiv-1-infection-and-integration
#8
Marina Lusic, Robert F Siliciano
To complete its life cycle, HIV-1 enters the nucleus of the host cell as reverse-transcribed viral DNA. The nucleus is a complex environment, in which chromatin is organized to support different structural and functional aspects of cell physiology. As such, it represents a challenge for an incoming viral genome, which needs to be integrated into cellular DNA to ensure productive infection. Integration of the viral genome into host DNA depends on the enzymatic activity of HIV-1 integrase and involves different cellular factors that influence the selection of integration sites...
December 12, 2016: Nature Reviews. Microbiology
https://www.readbyqxmd.com/read/27941595/achieving-hiv-1-control-through-rna-directed-gene-regulation
#9
REVIEW
Vera Klemm, Jye Mitchell, Christina Cortez-Jugo, Francesca Cavalieri, Geoff Symonds, Frank Caruso, Anthony Dominic Kelleher, Chantelle Ahlenstiel
HIV-1 infection has been transformed by combined anti-retroviral therapy (ART), changing a universally fatal infection into a controllable infection. However, major obstacles for an HIV-1 cure exist. The HIV latent reservoir, which exists in resting CD4+ T cells, is not impacted by ART, and can reactivate when ART is interrupted or ceased. Additionally, multi-drug resistance can arise. One alternate approach to conventional HIV-1 drug treatment that is being explored involves gene therapies utilizing RNA-directed gene regulation...
December 7, 2016: Genes
https://www.readbyqxmd.com/read/27928016/promising-role-of-toll-like-receptor-8-agonist-in-concert-with-prostratin-for-activation-of-silent-hiv
#10
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/27922055/limited-hiv-1-reactivation-in-resting-cd4-t-cells-from-aviremic-patients-under-protease-inhibitors
#11
Amit Kumar, Wasim Abbas, Sophie Bouchat, Jean-Stéphane Gatot, Sébastien Pasquereau, Kabamba Kabeya, Nathan Clumeck, Stéphane De Wit, Carine Van Lint, Georges Herbein
A latent viral reservoir that resides in resting CD4(+) T cells represents a major barrier for eradication of HIV infection. We test here the impact of HIV protease inhibitor (PI) based combination anti-retroviral therapy (cART) over nonnucleoside reverse transcriptase inhibitor (NNRTI)-based cART on HIV-1 reactivation and integration in resting CD4(+) T cells. This is a prospective cohort study of patients with chronic HIV-1 infection treated with conventional cART with an undetectable viremia. We performed a seven-year study of 47 patients with chronic HIV-infection treated with cART regimens and with undetectable plasma HIV-1 RNA levels for at least 1 year...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27905985/tlr7-8-agonist-induces-a-post-entry-samhd1-independent-block-to-hiv-1-infection-of-monocytes
#12
Henning Hofmann, Bénédicte Vanwalscappel, Nicolin Bloch, Nathaniel R Landau
BACKGROUND: Monocytes, the primary myeloid cell-type in peripheral blood, are resistant to HIV-1 infection as a result of the lentiviral restriction factor SAMHD1. Toll-like receptors recognize microbial pathogen components, inducing the expression of antiviral host proteins and proinflammatory cytokines. TLR agonists that mimic microbial ligands have been found to have activity against HIV-1 in macrophages. The induction of restriction factors in monocytes by TLR agonist activation has not been well studied...
December 1, 2016: Retrovirology
https://www.readbyqxmd.com/read/27898737/transcriptomic-analysis-implicates-the-p53-signaling-pathway-in-the-establishment-of-hiv-1-latency-in-central-memory-cd4-t-cells-in-an-in-vitro-model
#13
Cory H White, Bastiaan Moesker, Nadejda Beliakova-Bethell, Laura J Martins, Celsa A Spina, David M Margolis, Douglas D Richman, Vicente Planelles, Alberto Bosque, Christopher H Woelk
The search for an HIV-1 cure has been greatly hindered by the presence of a viral reservoir that persists despite antiretroviral therapy (ART). Studies of HIV-1 latency in vivo are also complicated by the low proportion of latently infected cells in HIV-1 infected individuals. A number of models of HIV-1 latency have been developed to examine the signaling pathways and viral determinants of latency and reactivation. A primary cell model of HIV-1 latency, which incorporates the generation of primary central memory CD4 T cells (TCM), full-length virus infection (HIVNL4-3) and ART to suppress virus replication, was used to investigate the establishment of HIV latency using RNA-Seq...
November 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27898590/reactivation-of-simian-immunodeficiency-virus-reservoirs-in-the-brain-of-virally-suppressed-macaques
#14
Lucio Gama, Celina M Abreu, Erin N Shirk, Sarah L Price, Ming Li, Greg M Laird, Kelly A Metcalf Pate, Stephen W Wietgrefe, Shelby L O'Connor, Luiz Pianowski, Ashley T Haase, Carine Van Lint, Robert F Siliciano, Janice E Clements
OBJECTIVE: Resting CD4 T cells have been recognized as the major cell reservoir of latent HIV-1 during antiretroviral therapy (ART). Using an simian immunodeficiency virus (SIV)/macaque model for AIDS and HIV-related neurocognitive disorders we assessed the contribution of the brain to viral latency and reactivation. DESIGN: Pigtailed macaques were dual inoculated with SIVDeltaB670 and SIV17E-Fr and treated with an efficacious central nervous system-penetrant ART...
January 2, 2017: AIDS
https://www.readbyqxmd.com/read/27898045/dendritic-cell-based-immunotherapies-to-fight-hiv-how-far-from-a-success-story-a-systematic-review-and-meta-analysis
#15
REVIEW
Antonio Victor Campos Coelho, Ronald Rodrigues de Moura, Anselmo Jiro Kamada, Ronaldo Celerino da Silva, Rafael Lima Guimarães, Lucas André Cavalcanti Brandão, Luiz Cláudio Arraes de Alencar, Sergio Crovella
The scientific community still faces the challenge of developing strategies to cure HIV-1. One of these pursued strategies is the development of immunotherapeutic vaccines based on dendritic cells (DCs), pulsed with the virus, that aim to boost HIV-1 specific immune response. We aimed to review DCs-based therapeutic vaccines reports and critically assess evidence to gain insights for the improvement of these strategies. We performed a systematic review, followed by meta-analysis and meta-regression, of clinical trial reports...
November 26, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27889530/identification-of-proximal-biomarkers-of-pkc-agonism-and-evaluation-of-their-role-in-hiv-reactivation
#16
Sai Vikram Vemula, Jill W Maxwell, Alexey Nefedov, Bang-Lin Wan, Justin Steve, William Newhard, Rosa I Sanchez, David Tellers, Richard J Barnard, Wade Blair, Daria Hazuda, Andrea L Webber, Bonnie J Howell
DESIGN: The HIV latent CD4(+) T cell reservoir is broadly recognized as a barrier to HIV cure. Induction of HIV expression using protein kinase C (PKC) agonists is one approach under investigation for reactivation of latently infected CD4(+) T cells (Beans et al., 2013; Abreu et al., 2014; Jiang et al., 2014; Jiang and Dandekar, 2015). We proposed that an increased understanding of the molecular mechanisms of action of PKC agonists was necessary to inform on biological signaling and pharmacodynamic biomarkers...
November 23, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27873219/immortalization-of-primary-microglia-a-new-platform-to-study-hiv-regulation-in-the-central-nervous-system
#17
Yoelvis Garcia-Mesa, Taylor R Jay, Mary Ann Checkley, Benjamin Luttge, Curtis Dobrowolski, Saba Valadkhan, Gary E Landreth, Jonathan Karn, David Alvarez-Carbonell
The major reservoirs for HIV in the CNS are in the microglia, perivascular macrophages, and to a lesser extent, astrocytes. To study the molecular events controlling HIV expression in the microglia, we developed a reliable and robust method to immortalize microglial cells from primary glia from fresh CNS tissues and commercially available frozen glial cells. Primary human cells, including cells obtained from adult brain tissue, were transformed with lentiviral vectors expressing SV40 T antigen or a combination of SVR40 T antigen and hTERT...
November 21, 2016: Journal of Neurovirology
https://www.readbyqxmd.com/read/27872306/paired-quantitative-and-qualitative-assessment-of-the-replication-competent-hiv-1-reservoir-and-comparison-with-integrated-proviral-dna
#18
Julio C C Lorenzi, Yehuda Z Cohen, Lillian B Cohn, Edward F Kreider, John P Barton, Gerald H Learn, Thiago Oliveira, Christy L Lavine, Joshua A Horwitz, Allison Settler, Mila Jankovic, Michael S Seaman, Arup K Chakraborty, Beatrice H Hahn, Marina Caskey, Michel C Nussenzweig
HIV-1-infected individuals harbor a latent reservoir of infected CD4(+) T cells that is not eradicated by antiretroviral therapy (ART). This reservoir presents the greatest barrier to an HIV-1 cure and has remained difficult to characterize, in part, because the vast majority of integrated sequences are defective and incapable of reactivation. To characterize the replication-competent reservoir, we have combined two techniques, quantitative viral outgrowth and qualitative sequence analysis of clonal outgrowth viruses...
December 6, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27858912/a-randomized-controlled-clinical-trial-on-the-impact-of-ccr5-blockade-with-maraviroc-in-early-infection-on-t-cell-dynamics
#19
Maile Y Karris, Anya Umlauf, Florin Vaida, Douglas Richman, Susan Little, Davey Smith
BACKGROUND: Initiation of antiretroviral therapy (ART) in early HIV infection demonstrates clinical benefits including enhanced CD4 T-lymphocyte recovery and minimization of the latent HIV reservoir. Whether ART intensification with CCR5 blockade provides additional benefits is unknown. TRIAL DESIGN: This randomized controlled trial evaluated the impact of maraviroc (MVC) intensification in persons starting ART in acute and early HIV (AEH, within 3 months of estimated date of infection)...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27855263/disruption-or-excision-of-provirus-as-an-approach-to-hiv-cure
#20
Keith R Jerome
An effective approach to HIV cure will almost certainly require a combination of strategies, including some means of reducing the latent HIV reservoir. Because the integrated HIV provirus represents the major source of viral persistence and reactivation, one attractive approach is the direct targeting of provirus for disruption or excision using targeted endonucleases, such as CRISPR/Cas9, zinc finger nucleases, TAL effector nucleases, or meganucleases (homing endonucleases). This article highlights some of the challenges for successful endonuclease therapy for HIV, including optimization of enzyme activity and specificity, the possible emergence of viral resistance, and most importantly, efficient in vivo delivery of the enzymes to a sufficient portion of the latent reservoir...
December 2016: AIDS Patient Care and STDs
keyword
keyword
44892
1
2
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"