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https://www.readbyqxmd.com/read/28934369/in-vivo-activation-of-latent-hiv-with-a-synthetic-bryostatin-analog-effects-both-latent-cell-kick-and-kill-in-strategy-for-virus-eradication
#1
Matthew D Marsden, Brian A Loy, Xiaomeng Wu, Christina M Ramirez, Adam J Schrier, Danielle Murray, Akira Shimizu, Steven M Ryckbosch, Katherine E Near, Tae-Wook Chun, Paul A Wender, Jerome A Zack
The ability of HIV to establish a long-lived latent infection within resting CD4+ T cells leads to persistence and episodic resupply of the virus in patients treated with antiretroviral therapy (ART), thereby preventing eradication of the disease. Protein kinase C (PKC) modulators such as bryostatin 1 can activate these latently infected cells, potentially leading to their elimination by virus-mediated cytopathic effects, the host's immune response and/or therapeutic strategies targeting cells actively expressing virus...
September 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28931091/mt-cell-responses-targeting-hiv-nef-uniquely-correlate-with-infected-cell-frequencies-after-long-term-antiretroviral-therapy
#2
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 20, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28926402/reversing-hiv-latency-via-sphingosine-1-phosphate-receptor-1-signaling
#3
Charline Duquenne, Sandrine Gimenez, Adeline Guigues, Benjamin Viala, Caroline Boulouis, Clément Mettling, Damien Maurel, Noëlie Campos, Etienne Doumazane, Laetitia Comps-Agrar, Jamal Tazi, Laurent Prézeau, Pierre Corbeau, Vincent François
OBJECTIVE: In this study, we looked for a new family of latency reversing agents. DESIGN: We searched for G protein-coupled receptors (GPCR) coexpressed with CCR5 in primary CD4+ T cells that activate infected cells and boost HIV production. METHODS: GPCR coexpression was unveiled by RT-PCR. We used FRET to analyze the dimerization with CCR5 of the expressed GPCR. Viral entry was measured by flow cytometry, reverse transcription by quantitative PCR, NFkB translocation by immunofluorescence, LTR activation using a gene reporter assay, and viral production by p24 quantification...
September 18, 2017: AIDS
https://www.readbyqxmd.com/read/28895782/dendritic-cells-as-natural-latency-reversing-agent-a-wake-up-call-for-hiv-1
#4
T van Montfort, D Speijer, B Berkhout
No abstract text is available yet for this article.
September 12, 2017: Virulence
https://www.readbyqxmd.com/read/28893280/eradication-of-hiv-1-latent-reservoirs-through-therapeutic-vaccination
#5
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/28890135/targeted-immune-interventions-for-an-hiv-1-cure
#6
REVIEW
Matthieu Perreau, Riddhima Banga, Giuseppe Pantaleo
Combination antiretroviral therapy (cART) induces durable suppression of virus replication but is unable to eradicate HIV. Invariably, virus rebound follows treatment interruption and life-long cART is thus required. Advances have been made in our understanding of HIV latency, identification of HIV cell reservoirs, regulation of HIV-specific immune responses, as well as in the development of broad neutralizing antibodies and putative therapeutic vaccines. These have provided a scientific basis to explore alternative strategies that achieve durable suppression of viremia in the absence of cART, the so-called functional cure...
September 7, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28882067/differentiating-immune-cell-targets-in-gut-associated-lymphoid-tissue-for-hiv-cure
#7
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/28878233/a-chalcone-derivative-reactivates-latent-hiv-1-transcription-through-activating-p-tefb-and-promoting-tat-sec-interaction-on-viral-promoter
#8
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
#9
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
#10
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/28865747/thalidomide-as-a-potential-hiv-latency-reversal-agent-is-it-the-right-time-to-forget-the-ancestral-sins
#11
Ramachandran Vignesh, Esaki M Shankar
No abstract text is available yet for this article.
August 30, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28864545/first-person-luca-sardo
#12
(no author information available yet)
First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Luca Sardo is co-first author on 'Real-time visualization of chromatin modification in isolated nuclei', published in Journal of Cell Science. Dr Sardo is a Postdoctoral Fellow at the Department of Biological Sciences, University of the Sciences in Philadelphia, investigating the mechanisms of HIV neuropathogenesis and latency...
September 1, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28852071/sonic-hedgehog-mimetic-prevents-leukocyte-infiltration-into-the-cns-during-acute-hiv-infection
#13
Vir B Singh, Meera V Singh, Dorota Piekna-Przybylska, Santhi Gorantla, Larisa Y Poluektova, Sanjay B Maggirwar
Infiltration of infected leukocytes culminates in establishment of a brain niche for Human Immunodeficiency Virus (HIV) during acute phase of infection, initiating an ongoing cascade of persistent viral replication and inflammation, that causes irreversible neuronal injury and HIV associated neurocognitive disease (HAND). In this study, humanized mice were treated with Smoothened Agonist (SAG), a Sonic Hedgehog (Shh) mimetic in order to fortify blood brain barrier (BBB) and dampen leukocyte extravasation into CNS during AHI...
August 29, 2017: Scientific Reports
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...
August 24, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28837714/change-in-pattern-of-secondary-cancers-after-kaposi-sarcoma-in-the-era-of-antiretroviral-therapy
#17
Fahad Mukhtar, Mmadili Ilozumba, Ovie Utuama, Oguz Cimenler
Importance: Studies performed in the 1980s and early 1990s have shown that people who develop Kaposi sarcoma (KS) are at higher risk of developing other cancers. The demographics of those affected with human immunodeficiency virus (HIV)/AIDS and KS have changed, and individuals with HIV/AIDS and KS now live longer. Objectives: To test the hypothesis that the secondary cancers developing in patients with KS have changed in recent years and to assess the risk of secondary cancers after KS in different periods...
August 24, 2017: JAMA Oncology
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/28827668/a-clue-to-unprecedented-strategy-to-hiv-eradication-lock-in-and-apoptosis
#19
Hiroshi Tateishi, Kazuaki Monde, Kensaku Anraku, Ryoko Koga, Yuya Hayashi, Halil Ibrahim Ciftci, Hasan DeMirci, Taishi Higashi, Keiichi Motoyama, Hidetoshi Arima, Masami Otsuka, Mikako Fujita
Despite the development of antiretroviral therapy against HIV, eradication of the virus from the body, as a means to a cure, remains in progress. A "kick and kill" strategy proposes "kick" of the latent HIV to an active HIV to eventually be "killed". Latency-reverting agents that can perform the "kick" function are under development and have shown promise. Management of the infected cells not to produce virions after the "kick" step is important to this strategy. Here we show that a newly synthesized compound, L-HIPPO, captures the HIV-1 protein Pr55(Gag) and intercepts its function to translocate the virus from the cytoplasm to the plasma membrane leading to virion budding...
August 21, 2017: Scientific Reports
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
#20
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...
August 12, 2017: EBioMedicine
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