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Latent hiv reservoir

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https://www.readbyqxmd.com/read/28937839/tza-a-novel-assay-for-measuring-the-latent-hiv-1-reservoir
#1
Phalguni Gupta, Anwesha Sanyal, Robbie B Mailliard
No abstract text is available yet for this article.
September 22, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28928214/fishing-out-the-hidden-enemy-advances-in-detecting-and-measuring-latent-hiv-infected-cells
#2
Vinayaka R Prasad, Ganjam V Kalpana
The indomitable aspect of HIV-1 infection is not that HIV-1 proviral DNA is integrated into host DNA but that it can also turn itself off, remaining invisible to drug or immune surveillance. Thus, the goals of eradication include ways to precisely excise HIV-1 DNA or wake up the silent HIV-1 provirus and eliminate the infected cells thus identified. Methods to identify and fish out the latently infected cells or to delineate their characteristics are being rapidly developed. In 2016, Baxter et al. (A. E. Baxter, J...
September 19, 2017: MBio
https://www.readbyqxmd.com/read/28915327/adipose-tissue-in-hiv-infection
#3
John R Koethe
HIV infection and antiretroviral therapy (ART) treatment exert diverse effects on adipocytes and stromal-vascular fraction cells, leading to changes in adipose tissue quantity, distribution, and energy storage. A HIV-associated lipodystrophic condition was recognized early in the epidemic, characterized by clinically apparent changes in subcutaneous, visceral, and dorsocervical adipose depots. Underlying these changes is altered adipose tissue morphology and expression of genes central to adipocyte maturation, regulation, metabolism, and cytokine signaling...
September 12, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28894444/modeling-kick-kill-strategies-toward-hiv-cure
#4
REVIEW
Esteban A Hernandez-Vargas
Although combinatorial antiretroviral therapy (cART) potently suppresses the virus, a sterile or functional cure still remains one of the greatest therapeutic challenges worldwide. Reservoirs are infected cells that can maintain HIV persistence for several years in patients with optimal cART, which is a leading obstacle to eradicate the virus. Despite the significant progress that has been made in our understanding of the diversity of cells that promote HIV persistence, many aspects that are critical to the development of effective therapeutic approaches able to purge the latent CD4+ T cell reservoir are poorly understood...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28893281/rna-flow-cytometric-fish-for-investigations-into-hiv-immunology-vaccination-and-cure-strategies
#5
REVIEW
Amy E Baxter, Julia Niessl, Antigoni Morou, Daniel E Kaufmann
Despite the tremendous success of anti-retroviral therapy (ART) no current treatment can eradicate latent HIV reservoirs from HIV-infected individuals or generate, effective HIV-specific immunity. Technological limitations have hampered the identification and characterization of both HIV-infected cells and HIV-specific responses in clinical samples directly ex vivo. RNA-flow cytometric fluorescence in situ hybridisation (RNA Flow-FISH) is a powerful technique, which enables detection of mRNAs in conjunction with proteins at a single-cell level...
September 12, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28893280/eradication-of-hiv-1-latent-reservoirs-through-therapeutic-vaccination
#6
REVIEW
Joshua Pankrac, Katja Klein, Jamie F S Mann
Despite the significant success of combination anti-retroviral therapy to reduce HIV viremia and save lives, HIV-1 infection remains a lifelong infection that must be appropriately managed. Advances in the understanding of the HIV infection process and insights from vaccine development in other biomedical fields such as cancer, imaging, and genetic engineering have fueled rapid advancements in HIV cure research. In the last few years, several studies have focused on the development of "Kick and Kill" therapies to reverse HIV latency and kick start viral translational activity...
September 12, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28892313/-hiv-cure-a-realistic-perspective
#7
G Darcis, M Moutschen
More than 30 years after its discovery, human immunodeficiency virus (HIV) continues to be a major global public health issue. Antiretroviral therapy increases survival and quality of life of HIV-infected patients but is not curative. Indeed, interruption of therapy invariably leads to the re-emergence of detectable viral replication, since HIV persists in extremely long-lived viral latent reservoirs. Those viral latent reservoirs constitute the major source of viral recovery following antiretroviral treatment interruption and are considered as the most important hurdle to HIV eradication...
September 2017: Revue Médicale de Liège
https://www.readbyqxmd.com/read/28882067/differentiating-immune-cell-targets-in-gut-associated-lymphoid-tissue-for-hiv-cure
#8
Shahzada Khan, Sushama Telwatte, Martin Trapecar, Steven Yukl, Shomyseh Sanjabi
The single greatest challenge to an HIV cure is the persistence of latently-infected cells containing inducible, replication-competent proviral genomes that constitute only a small fraction of total or infected cells in the body. Although resting CD4+ T cells in the blood are a well-known source of viral rebound, more than 90% of the body's lymphocytes reside elsewhere. Many are in gut tissue, where HIV DNA levels per million CD4+ T cells are considerably higher than in the blood. Despite the significant contribution of gut tissue to viral replication and persistence, little is known about the cell types that support persistence of HIV in the gut; importantly, T cells in the gut have phenotypic, functional, and survival properties that are distinct from T cells in other tissues...
September 7, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28880280/multiparametric-characterization-of-rare-hiv-infected-cells-using-an-rna-flow-fish-technique
#9
Amy E Baxter, Julia Niessl, Rémi Fromentin, Jonathan Richard, Filippos Porichis, Marta Massanella, Nathalie Brassard, Nirmin Alsahafi, Jean-Pierre Routy, Andrés Finzi, Nicolas Chomont, Daniel E Kaufmann
Efforts to cure HIV are hampered by limited characterization of the cells supporting HIV replication in vivo and inadequate methods for quantifying the latent viral reservoir in individuals receiving antiretroviral therapy (ART). We describe a protocol for flow cytometric identification of viral reservoirs, based on concurrent detection of cellular HIV Gagpol mRNA by in situ RNA hybridization combined with antibody staining for the HIV Gag protein. By simultaneously detecting both HIV RNA and protein, the CD4 T cells harboring translation-competent virus can be identified...
October 2017: Nature Protocols
https://www.readbyqxmd.com/read/28878233/a-chalcone-derivative-reactivates-latent-hiv-1-transcription-through-activating-p-tefb-and-promoting-tat-sec-interaction-on-viral-promoter
#10
Jun Wu, Ming-Tao Ao, Rui Shao, Hui-Ru Wang, Diao Yu, Mei-Juan Fang, Xiang Gao, Zhen Wu, Qiang Zhou, Yu-Hua Xue
The principal barrier to the eradication of HIV/AIDS is the existence of latent viral reservoirs. One strategy to overcome this barrier is to use latency-reversing agents (LRAs) to reactivate the latent proviruses, which can then be eliminated by effective anti-retroviral therapy. Although a number of LRAs have been found to reactivate latent HIV, they have not been used clinically due to high toxicity and poor efficacy. In this study, we report the identification of a chalcone analogue called Amt-87 that can significantly reactivate the transcription of latent HIV provirses and act synergistically with known LRAs such as prostratin and JQ1 to reverse latency...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28878119/pharmacologic-hiv-1-nef-blockade-promotes-cd8-t-cell-mediated-elimination-of-latently-hiv-1-infected-cells-in-vitro
#11
Shariq Mujib, Aamir Saiyed, Saleh Fadel, Ardalan Bozorgzad, Nasra Aidarus, Feng Yun Yue, Erika Benko, Colin Kovacs, Lori A Emert-Sedlak, Thomas E Smithgall, Mario A Ostrowski
Eradication of the HIV-1 latent reservoir represents the current paradigm to developing a cure for AIDS. HIV-1 has evolved multiple mechanisms to evade CD8 T cell responses, including HIV-1 Nef-mediated downregulation of MHC-I from the surface of infected cells. Nef transcripts and protein are detectable in samples from aviremic donors, suggesting that Nef expression in latently HIV-1-infected CD4 T cells protects them from immune-mediated clearance. Here, we tested 4 small molecule inhibitors of HIV-1 Nef in an in vitro primary CD4 T cell latency model and measured the ability of autologous ex vivo or HIV-1 peptide-expanded CD8 T cells to recognize and kill latently infected cells as a function of inhibitor treatment...
September 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/28874382/evaluation-of-the-innate-immune-modulator-acitretin-as-a-strategy-to-clear-the-hiv-reservoir
#12
Edurne Garcia-Vidal, Marc Castellví, Maria Pujantell, Roger Badia, Antoni Jou, Lucia Gomez, Teresa Puig, Bonaventura Clotet, Ester Ballana, Eva Riveira-Muñoz, José A Esté
The persistence of HIV despite suppressive antiretroviral therapy is a major roadblock to HIV eradication. Current strategies focused on inducing the expression of latent HIV fail to clear the persistent reservoir, prompting the development of new approaches for killing HIV+ cells. Recently, acitretin has been proposed as a pharmacological innate cellular-defense network enhancer that led to virus reactivation and preferential death of infected cells. We have evaluated the capacity of acitretin to reactivate and/or facilitate immune-mediated clearance of HIV+ cells...
September 5, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28862291/trans-activation-response-element-rna-is-detectable-in-the-plasma-of-a-subset-of-aviremic-hiv-1-infected-patients
#13
Anžej Hladnik, Jana Ferdin, Katja Goričar, G Steven Deeks, M Boris Peterlin, Ana Plemenitaš, Dolžan Vita, Lenassi Metka
Determining the HIV-1 reservoir size in infected individuals is of great importance for improvement of their treatment. Plasma trans-activation response element (TAR) RNA has been suggested as one of the possible biomarkers. TAR RNA is produced during non-processive transcription in HIV-1 productively infected and latent T cells. Here, plasma samples and paired exosome samples of 55 subjects from the observational SCOPE cohort were analysed for the presence of TAR RNA. First, a PCR-based assay was optimized, which provided 100% specificity and 100% sensitivity in differentiating HIV-1 infected non-controllers from uninfected individuals...
September 2017: Acta Chimica Slovenica
https://www.readbyqxmd.com/read/28858725/focus-on-the-therapeutic-efficacy-of-3bnc117-against-hiv-1-in-vitro-studies-in-vivo-studies-clinical-trials-and-challenges
#14
REVIEW
Zhi-Jun Liu, Jing Bai, Feng-Li Liu, Xiang-Yang Zhang, Jing-Zhang Wang
3BNC117, which was discovered in 2011, is a broadly neutralizing antibody (bNAb) and specifically neutralizes the human immunodeficiency virus type-1 (HIV-1) by targeting the CD4-binding site. This is the first comprehensive review that focuses on the role of 3BNC117 in the prevention of HIV-1 and acquired immune deficiency syndrome (AIDS). Briefly, 3BNC117 neutralizes many HIV/SHIV strains in vitro, blocks HIV-1 acquisition in animal models via a pre-exposure prophylaxis, alleviates HIV-1-associated viremia via a post-exposure therapeutic effect, prevents the establishment of latent HIV-1 reservoirs, and induces both humoral and cellular anti-HIV immune responses in vivo...
August 28, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28851294/landscape-review-of-current-hiv-kick-and-kill-cure-research-some-kicking-not-enough-killing
#15
REVIEW
Kristian Thorlund, Marc S Horwitz, Brian T Fife, Richard Lester, D William Cameron
BACKGROUND: Current antiretroviral therapy (ART) used to treat human immunodeficiency virus (HIV) patients is life-long because it only suppresses de novo infections. Recent efforts to eliminate HIV have tested the ability of a number of agents to reactivate ('Kick') the well-known latent reservoir. This approach is rooted in the assumption that once these cells are reactivated the host's immune system itself will eliminate ('Kill') the virus. While many agents have been shown to reactivate large quantities of the latent reservoir, the impact on the size of the latent reservoir has been negligible...
August 29, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28842560/reactivation-of-hiv-1-from-latency-by-an-ingenol-derivative-from-euphorbia-kansui
#16
Pengfei Wang, Panpan Lu, Xiying Qu, Yinzhong Shen, Hanxian Zeng, Xiaoli Zhu, Yuqi Zhu, Xian Li, Hao Wu, Jianqing Xu, Hongzhou Lu, Zhongjun Ma, Huanzhang Zhu
Cells harboring latent HIV-1 pose a major obstacle to eradication of the virus. The 'shock and kill' strategy has been broadly explored to purge the latent reservoir; however, none of the current latency-reversing agents (LRAs) can safely and effectively activate the latent virus in patients. In this study, we report an ingenol derivative called EK-16A, isolated from the traditional Chinese medicinal herb Euphorbia kansui, which displays great potential in reactivating latent HIV-1. A comparison of the doses used to measure the potency indicated EK-16A to be 200-fold more potent than prostratin in reactivating HIV-1 from latently infected cell lines...
August 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28842263/screening-of-an-fda-approved-compound-library-identifies-levosimendan-as-a-novel-anti-hiv-1-agent-that-inhibits-viral-transcription
#17
Tsuyoshi Hayashi, Maxime Jean, Huachao Huang, Sydney Simpson, Netty G Santoso, Jian Zhu
Combination antiretroviral therapy (cART) has been proven to efficiently inhibit ongoing replication of human immunodeficiency virus type 1 (HIV-1), and significantly improve the health outcome in patients of acquired immune deficiency syndrome (AIDS). However, cART is unable to cure HIV-1/AIDS. Even in presence of cART there exists a residual viremia, contributed from the viral reservoirs of latently infected HIV-1 proviruses; this constitutes a major hurdle. Currently, there are multiple strategies aimed at eliminating or permanently silence these HIV-1 latent reservoirs being intensely explored...
August 24, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28835903/flow-cytometric-analysis-of-drug-induced-hiv-1-transcriptional-activity-in-a2-and-a72-j-lat-cell-lines
#18
Daniela Boehm, Melanie Ott
The main obstacle to eradicating HIV-1 from patients is post-integration latency (Finzi et al., 1999). Antiretroviral treatments target only actively replicating virus, while latent infections that have low or no transcriptional activity remain untreated (Sedaghat et al., 2007). A combination of antiretroviral treatments with latency-purging strategies may accelerate the depletion of latent reservoirs and lead to a cure (Geeraert et al., 2008). Current strategies to reactivate HIV-1 from latency include use of prostratin, a non-tumor-promoting phorbol ester (Williams et al...
May 20, 2017: Bio-protocol
https://www.readbyqxmd.com/read/28814661/hdac-inhibition-induces-hiv-1-protein-and-enables-immune-based-clearance-following-latency-reversal
#19
Guoxin Wu, Michael Swanson, Aarthi Talla, Donald Graham, Julie Strizki, Daniel Gorman, Richard Jo Barnard, Wade Blair, Ole S Søgaard, Martin Tolstrup, Lars Østergaard, Thomas A Rasmussen, Rafick-Pierre Sekaly, Nancie M Archin, David M Margolis, Daria J Hazuda, Bonnie J Howell
Promising therapeutic approaches for eradicating HIV include transcriptional activation of provirus from latently infected cells using latency-reversing agents (LRAs) and immune-mediated clearance to purge reservoirs. Accurate detection of cells capable of producing viral antigens and virions, and the measurement of clearance of infected cells, is essential to assessing therapeutic efficacy. Here, we apply enhanced methodology extending the sensitivity limits for the rapid detection of subfemtomolar HIV gag p24 capsid protein in CD4+ T cells from ART-suppressed HIV+ individuals, and we show viral protein induction following treatment with LRAs...
August 17, 2017: JCI Insight
https://www.readbyqxmd.com/read/28811349/brain-macrophages-in-simian-immunodeficiency-virus-infected-antiretroviral-suppressed-macaques-a-functional-latent-reservoir
#20
Claudia R Avalos, Celina M Abreu, Suzanne E Queen, Ming Li, Sarah Price, Erin N Shirk, Elizabeth L Engle, Ellen Forsyth, Brandon T Bullock, Feilim Mac Gabhann, Stephen W Wietgrefe, Ashley T Haase, M Christine Zink, Joseph L Mankowski, Janice E Clements, Lucio Gama
A human immunodeficiency virus (HIV) infection cure requires an understanding of the cellular and anatomical sites harboring virus that contribute to viral rebound upon treatment interruption. Despite antiretroviral therapy (ART), HIV-associated neurocognitive disorders (HAND) are reported in HIV-infected individuals on ART. Biomarkers for macrophage activation and neuronal damage in cerebrospinal fluid (CSF) of HIV-infected individuals demonstrate continued effects of HIV in brain and suggest that the central nervous system (CNS) may serve as a viral reservoir...
August 15, 2017: MBio
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