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HIV latency reactivation

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https://www.readbyqxmd.com/read/29142313/effects-of-exosome-on-the-activation-of-cd4-t-cells-in-rhesus-macaques-a-potential-application-for-hiv-latency-reactivation
#1
Xiaowu Hong, Blake Schouest, Huanbin Xu
Exosomes are small extracellular vesicles (EVs), released by a wide variety of cell types, carry donor origin-proteins, cytokines, and nucleic acids, transport these cargos to adjacent or distant specific recipient cells, and thereby regulate gene expression and activation of target cells. In this study, we isolated and identified exosomes in rhesus macaques, and investigated their effects on cell tropism and activation, especially their potential to reactivate HIV latency. The results indicated that plasma-derived exosomes preferentially fuse to TCR-activated T cells and autologous parent cells...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29135580/wake-me-up-before-you-go-a-strategy-to-reduce-the-latent-hiv-reservoir
#2
Nicolas Chomont, Afam A Okoye, David Favre, Lydie Trautmann
: In the quest to eliminate or reduce the HIV reservoir, shock and kill strategies require the combined administration of a latency reversing agent (LRA) to reactivate the latent reservoir and an intervention to boost effector functions to clear this reservoir. Both parts of this strategy are quite inefficient when LRAs are administered to HIV-infected individuals on suppressive ART for several years, possibly due to low levels of induced antigen expression, negative impact of LRAs on clearance mechanisms, and very low number of effective cytotoxic T cells (CTLs)...
November 10, 2017: AIDS
https://www.readbyqxmd.com/read/29118123/estimating-initial-viral-levels-during-hiv-siv-reactivation-from-latency
#3
Mykola Pinkevych, Christine M Fennessey, Deborah Cromer, Martin Tolstrup, Ole S Søgaard, Thomas A Rasmussen, Brandon F Keele, Miles P Davenport
HIV viremia rebounds rapidly after treatment interruption, and a variety of strategies are being explored to reduce or control viral reactivation post-treatment. This viral rebound arises from reactivation of individual latently infected cells, which spread during ongoing rounds of productive infection. The level of virus produced by the initial individual reactivating cells is not known, although it may have major implications for the ability of different immune interventions to control viral rebound. Here we use data from both HIV and SIV treatment interruption studies to estimate the initial viral load post-interruption and thereby the initial individual reactivation event...
November 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29099677/novel-latency-reversal-agents-for-hiv-1-cure
#4
Adam M Spivak, Vicente Planelles
Antiretroviral therapy (ART) has rendered HIV-1 infection a treatable illness; however, ART is not curative owing to the persistence of replication-competent, latent proviruses in long-lived restingTcells. Strategies that target these latently infected cells and allow immune recognition and clearance of this reservoir will be necessary to eradicate HIV-1 in infected individuals. This review describes current pharmacologic approaches to reactivate the latent reservoir so that infected cells can be recognized and targeted, with the ultimate goal of achieving an HIV-1 cure...
November 3, 2017: Annual Review of Medicine
https://www.readbyqxmd.com/read/29089933/curaxin-cbl0100-blocks-hiv-1-replication-and-reactivation-through-inhibition-of-viral-transcriptional-elongation
#5
Maxime J Jean, Tsuyoshi Hayashi, Huachao Huang, Justin Brennan, Sydney Simpson, Andrei Purmal, Katerina Gurova, Michael C Keefer, James J Kobie, Netty G Santoso, Jian Zhu
Despite combination antiretroviral therapy (cART), acquired immunodeficiency syndrome (AIDS), predominantly caused by the human immunodeficiency virus type 1 (HIV-1), remains incurable. The barrier to a cure lies in the virus' ability to establish a latent infection in HIV/AIDS patients. Unsurprisingly, efforts for a sterilizing cure have focused on the "shock and kill" strategy using latency-reversing agents (LRAs) to complement cART in order to eliminate these latent reservoirs. However, this method faces numerous challenges...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29071475/assays-to-measure-latency-reservoirs-and-reactivation
#6
Janet D Siliciano, Robert F Siliciano
HIV-1 persists even in patients who are successfully treated with combination antiretroviral therapy. The major barrier to cure is a small pool of latently infected resting CD4(+) T cells carrying an integrated copy of the viral genome that is not expressed while the cells remain in a resting state. Targeting this latent reservoir is a major focus of HIV-1 cure research, and the development of a rapid and scalable assay for the reservoir is a rate-limiting step in the search for a cure. The most commonly used assays are standard PCR assays targeting conserved regions of the HIV-1 genome...
October 26, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/29046460/myeloid-dendritic-cells-repress-human-cytomegalovirus-gene-expression-and-spread-by-releasing-interferon-unrelated-soluble-antiviral-factors
#7
Bahram Kasmapour, Tobias Kubsch, Ulfert Rand, Britta Eiz-Vesper, Martin Messerle, Florian W R Vondran, Bettina Wiegmann, Axel Haverich, Luka Cicin-Sain
Cytomegalovirus (CMV) is a beta-herpesvirus that latently infects most adult humans worldwide and is a major cause of morbidity and mortality in immunocompromised hosts. Latent human CMV (HCMV) is believed to reside in precursors of myeloid-lineage, leukocytes and monocytes, which give raise to macrophages and dendritic cells. We report here that human monocyte derived DCs (mo-DC) suppress HCMV infection in coculture with infected fibroblasts target cells in an effector-to-target-ratio dependent manner. Intriguingly, optimal activation of mo-DC was achieved in coculture conditions, not by their direct infection with HCMV, implying that mo-DC may recognize unique molecular patterns on, or within, infected fibroblasts...
October 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29027985/triterpenoids-from-ocimum-labiatum-activates-latent-hiv-1-expression-in-vitro-potential-for-use-in-adjuvant-therapy
#8
Petrina Kapewangolo, Justin J Omolo, Pascaline Fonteh, Martha Kandawa-Schulz, Debra Meyer
Latent HIV reservoirs in infected individuals prevent current treatment from eradicating infection. Treatment strategies against latency involve adjuvants for viral reactivation which exposes viral particles to antiretroviral drugs. In this study, the effect of novel triterpenoids isolated from Ocimum labiatum on HIV-1 expression was measured through HIV-1 p24 antigen capture in the U1 latency model of HIV-1 infection and in peripheral blood mononuclear cells (PBMCs) of infected patients on combination antiretroviral therapy (cART)...
October 13, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29021396/quiescence-promotes-latent-hiv-infection-and-resistance-to-reactivation-from-latency-with-histone-deacetylase-inhibitors
#9
Mark M Painter, Thomas D Zaikos, Kathleen L Collins
Human immunodeficiency virus type-1 (HIV-1) establishes transcriptionally silent latent infections in many cell types, including resting memory T cells and hematopoietic stem and progenitor cells (HSPCs), which allow the virus to persist in infected individuals despite antiretroviral therapy. Developing in vitro models of HIV-1 latency that recapitulate the characteristics of latently-infected cells in vivo is crucial to identifying and developing effective latency-reversing therapies. HSPCs exist in a quiescent state in vivo, and quiescence is correlated with latent infections in T cells...
October 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28949981/mycobacterium-tuberculosis-reactivates-latent-hiv-1-in-t-cells-in-vitro
#10
Erica C Larson, Camille L Novis, Laura J Martins, Amanda B Macedo, Kadyn E Kimball, Alberto Bosque, Vicente Planelles, Louis R Barrows
Following proviral integration into the host cell genome and establishment of a latent state, the human immunodeficiency virus type 1 (HIV-1) can reenter a productive life cycle in response to various stimuli. HIV-1 reactivation occurs when transcription factors, such as nuclear factor-κB (NF-κB), nuclear factor of activated T cells (NFAT), and activator protein -1 (AP-1), bind cognate sites within the long terminal repeat (LTR) region of the HIV-1 provirus to promote transcription. Interestingly, pattern recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs) can reactivate latent HIV-1 through activation of the transcription factor NF-κB...
2017: PloS One
https://www.readbyqxmd.com/read/28931091/t-cell-responses-targeting-hiv-nef-uniquely-correlate-with-infected-cell-frequencies-after-long-term-antiretroviral-therapy
#11
Allison S Thomas, Kimberley L Jones, Rajesh T Gandhi, Deborah K McMahon, Joshua C Cyktor, Dora Chan, Szu-Han Huang, Ronald Truong, Alberto Bosque, Amanda B Macedo, Colin Kovacs, Erika Benko, Joseph J Eron, Ronald J Bosch, Christina M Lalama, Samuel Simmens, Bruce D Walker, John W Mellors, R Brad Jones
HIV-specific CD8+ T-cell responses limit viral replication in untreated infection. After the initiation of antiretroviral therapy (ART), these responses decay and the infected cell population that remains is commonly considered to be invisible to T-cells. We hypothesized that HIV antigen recognition may persist in ART-treated individuals due to low-level or episodic protein expression. We posited that if persistent recognition were occurring it would be preferentially directed against the early HIV gene products Nef, Tat, and Rev as compared to late gene products, such as Gag, Pol, and Env, which have higher barriers to expression...
September 2017: PLoS Pathogens
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
#12
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/28874382/evaluation-of-the-innate-immune-modulator-acitretin-as-a-strategy-to-clear-the-hiv-reservoir
#13
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-positive cells. Recently, acitretin was proposed as a pharmacological enhancer of the innate cellular defense network that led to virus reactivation and preferential death of infected cells. We evaluated the capacity of acitretin to reactivate and/or to facilitate immune-mediated clearance of HIV-positive cells...
November 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28844864/the-short-isoform-of-brd4-promotes-hiv-1-latency-by-engaging-repressive-swi-snf-chromatin-remodeling-complexes
#14
Ryan J Conrad, Parinaz Fozouni, Sean Thomas, Hendrik Sy, Qiang Zhang, Ming-Ming Zhou, Melanie Ott
BET proteins commonly activate cellular gene expression, yet inhibiting their recruitment paradoxically reactivates latent HIV-1 transcription. Here we identify the short isoform of BET family member BRD4 (BRD4S) as a corepressor of HIV-1 transcription. We found that BRD4S was enriched in chromatin fractions of latently infected T cells, and it was more rapidly displaced from chromatin upon BET inhibition than the long isoform. BET inhibition induced marked nucleosome remodeling at the latent HIV-1 promoter, which was dependent on the activity of BRG1-associated factors (BAF), an SWI/SNF chromatin-remodeling complex with known repressive functions in HIV-1 transcription...
September 21, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28842560/reactivation-of-hiv-1-from-latency-by-an-ingenol-derivative-from-euphorbia-kansui
#15
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
#16
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...
October 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
#17
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/28822719/thalidomide-is-associated-with-increased-t-cell-activation-and-inflammation-in-antiretroviral-naive-hiv-infected-individuals-in-a-randomised-clinical-trial-of-efficacy-and-safety
#18
Tânia R C Vergara, Sadia Samer, Joanna R Santos-Oliveira, Leila B Giron, Muhammad Shoaib Arif, Maria Luciana Silva-Freitas, Lia A Cherman, Mauro S Treitsman, Alberto Chebabo, Maria Cecilia A Sucupira, Alda M Da-Cruz, Ricardo Sobhie Diaz
TRIAL DESIGN: Open-label, randomised, controlled, pilot proof-of-concept clinical trial. METHODS: Participants: Antiretroviral naïve adult males with CD4 count ≥350cells/mm(3). INTERVENTIONS: Patients were randomised to receive thalidomide 200mg QD for 3weeks (Thalidomide group) or not (Control group) and followed for 48weeks. OBJECTIVE: We hypothesized that short-term Thalidomide use would reduce HIV related inflammation and HIV replication among antiretroviral naïve HIV infected individuals...
September 2017: EBioMedicine
https://www.readbyqxmd.com/read/28794022/potent-in-vivo-nk-cell-mediated-elimination-of-hiv-1-infected-cells-mobilized-by-a-gp120-bispecific-and-hexavalent-broadly-neutralizing-fusion-protein
#19
Ariola Bardhi, Yanling Wu, Weizao Chen, Wei Li, Zhongyu Zhu, Jian Hua Zheng, Hing Wong, Emily Jeng, Jennifer Jones, Christina Ochsenbauer, John C Kappes, Dimiter S Dimitrov, Tianlei Ying, Harris Goldstein
Antibodies bound to human immunodeficiency virus type 1 (HIV-1) envelope protein expressed by infected cells mobilize antibody-dependent cellular cytotoxicity (ADCC) to eliminate the HIV-1-infected cells and thereby suppress HIV-1 infection and delay disease progression. Studies treating HIV-1-infected individuals with latency reactivation agents to reduce their latent HIV-1 reservoirs indicated that their HIV-1-specific immune responses were insufficient to effectively eliminate the reactivated latent HIV-1-infected T cells...
October 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28782474/the-relevance-of-post-transcriptional-mechanisms-in-hiv-latency-reversal
#20
Ambra Sarracino, Alessandro Marcello
BACKGROUND: Infection by the human immunodeficiency virus has become a curable disease, which could not be cured because the virus persists in the face of an efficacious drug treatment. Current efforts for the rescue of replication-competent virus from cellular reservoirs are limited to drugs targeting transcriptional reactivation of the dormant virus and clinical trials so far are disappointing. One explanation could be that post-transcriptional pathways are not optimal thus impeding full reactivation of the virus, which is required for purging the cellular reservoirs...
August 3, 2017: Current Pharmaceutical Design
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