keyword
MENU ▼
Read by QxMD icon Read
search

HIV latency reactivation

keyword
https://www.readbyqxmd.com/read/29789664/the-bet-bromodomain-inhibitor-apabetalone-induces-apoptosis-of-latent-hiv-1-reservoir-cells-following-viral-reactivation
#1
Xuan-Xuan Zhang, Jian Lin, Tai-Zhen Liang, Heng Duan, Xing-Hua Tan, Bao-Min Xi, Lin Li, Shu-Wen Liu
The persistence of latent HIV-1 reservoirs throughout combination antiretroviral therapy (cART) is a major barrier on the path to achieving a cure for AIDS. It has been shown that bromodomain and extra-terminal (BET) inhibitors could reactivate HIV-1 latency, but restrained from clinical application due to their toxicity and side effects. Thus, identifying a new type of BET inhibitor with high degrees of selectivity and safety is urgently needed. Apabetalone is a small-molecule selective BET inhibitor specific for second bromodomains, and has been evaluated in phase III clinical trials that enrolled patients with high-risk cardiovascular disorders, dyslipidemia, and low HDL cholesterol...
May 22, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29770863/siv-latency-in-macrophages-in-the-cns
#2
Lucio Gama, Celina Abreu, Erin N Shirk, Suzanne E Queen, Sarah E Beck, Kelly A Metcalf Pate, Brandon T Bullock, M Christine Zink, Joseph L Mankowski, Janice E Clements
Lentiviruses infect myeloid cells, leading to acute infection followed by persistent/latent infections not cleared by the host immune system. HIV and SIV are lentiviruses that infect CD4+ lymphocytes in addition to myeloid cells in blood and tissues. HIV infection of myeloid cells in brain, lung, and heart causes tissue-specific diseases that are mostly observed during severe immunosuppression, when the number of circulating CD4+ T cells declines to exceeding low levels. Antiretroviral therapy (ART) controls viral replication but does not successfully eliminate latent virus, which leads to viral rebound once ART is interrupted...
May 17, 2018: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/29762173/a-defucosylated-bispecific-multivalent-molecule-exhibits-broad-hiv-1-neutralizing-activity-and-enhanced-adcc-against-reactivated-hiv-1-latently-infected-cells
#3
Desheng Kong, Yan Wang, Ping Ji, Wei Li, Tianlei Ying, Jinghe Huang, Chen Wang, Yanling Wu, Yanping Wang, Weizao Chen, Yanling Hao, Kunxue Hong, Yiming Shao, Dimiter S Dimitrov, Shibo Jiang, Liying Ma
OBJECTIVE: Current treatments cannot completely eradicate HIV-1 owing to the presence of latently infected cells which harbor transcriptionally silent HIV-1. However, defucosylated antibodies can readily kill latently infected cells after their activation to express envelope glycoprotein (Env) through antibody-dependent cellular cytotoxicity (ADCC). We herein aimed to test a defucosylated bispecific multivalent molecule consisting of domain-antibody and single-domain CD4, LSEVh-LS-F, for its HIV-1 neutralizing activity and ADCC against the reactivated latently infected cells, compared with the non-defucosylated molecule LSEVh-LS...
May 11, 2018: AIDS
https://www.readbyqxmd.com/read/29751762/hiv-latency-reversing-agents-act-through-tat-post-translational-modifications
#4
Georges Khoury, Talia M Mota, Shuang Li, Carolin Tumpach, Michelle Y Lee, Jonathan Jacobson, Leigh Harty, Jenny L Anderson, Sharon R Lewin, Damian F J Purcell
BACKGROUND: Different classes of latency reversing agents (LRAs) are being evaluated to measure their effects in reactivating HIV replication from latently infected cells. A limited number of studies have demonstrated additive effects of LRAs with the viral protein Tat in initiating transcription, but less is known about how LRAs interact with Tat, particularly through basic residues that may be post-translationally modified to alter the behaviour of Tat for processive transcription and co-transcriptional RNA processing...
May 11, 2018: Retrovirology
https://www.readbyqxmd.com/read/29717016/sun2-modulates-hiv-1-infection-and-latency-through-association-with-lamin-a-c-to-maintain-the-repressive-chromatin
#5
Wei-Wei Sun, Shi Jiao, Li Sun, Zhaocai Zhou, Xia Jin, Jian-Hua Wang
The postintegrational latency of HIV-1 is characterized by reversible silencing of long terminal repeat (LTR)-driven transcription of the HIV genome. It is known that the formation of repressive chromatin at the 5'-LTR of HIV-1 proviral DNA impedes viral transcription by blocking the recruitment of positive transcription factors. How the repressive chromatin is formed and modulated during HIV-1 infection remains elusive. Elucidation of which chromatin reassembly factor mediates the reorganization of chromatin is likely to facilitate the understanding of the host's modulation of HIV-1 transcription and latency...
May 1, 2018: MBio
https://www.readbyqxmd.com/read/29714165/distinct-chromatin-functional-states-correlate-with-hiv-latency-reactivation-in-infected-primary-cd4-t-cells
#6
Emilie Battivelli, Matthew S Dahabieh, Mohamed Abdel-Mohsen, J Peter Svensson, Israel Tojal Da Silva, Lillian B Cohn, Andrea Gramatica, Steven Deeks, Warner C Greene, Satish K Pillai, Eric Verdin
Human immunodeficiency virus (HIV) infection is currently incurable, due to the persistence of latently infected cells. The 'shock and kill' approach to a cure proposes to eliminate this reservoir via transcriptional activation of latent proviruses, enabling direct or indirect killing of infected cells. Currently available latency-reversing agents (LRAs) have however proven ineffective. To understand why, we used a novel HIV reporter strain in primary CD4+ T cells and determined which latently infected cells are reactivatable by current candidate LRAs...
May 1, 2018: ELife
https://www.readbyqxmd.com/read/29694901/single-cell-rna-seq-reveals-transcriptional-heterogeneity-in-latent-and-reactivated-hiv-infected-cells
#7
Monica Golumbeanu, Sara Cristinelli, Sylvie Rato, Miguel Munoz, Matthias Cavassini, Niko Beerenwinkel, Angela Ciuffi
Despite effective treatment, HIV can persist in latent reservoirs, which represent a major obstacle toward HIV eradication. Targeting and reactivating latent cells is challenging due to the heterogeneous nature of HIV-infected cells. Here, we used a primary model of HIV latency and single-cell RNA sequencing to characterize transcriptional heterogeneity during HIV latency and reactivation. Our analysis identified transcriptional programs leading to successful reactivation of HIV expression.
April 24, 2018: Cell Reports
https://www.readbyqxmd.com/read/29684085/the-kat5-acetyl-histone4-brd4-axis-silences-hiv-1-transcription-and-promotes-viral-latency
#8
Zichong Li, Uri Mbonye, Zeming Feng, Xiaohui Wang, Xiang Gao, Jonathan Karn, Qiang Zhou
The bromodomain protein Brd4 promotes HIV-1 latency by competitively inhibiting P-TEFb-mediated transcription induced by the virus-encoded Tat protein. Brd4 is recruited to the HIV LTR by interactions with acetyl-histones3 (AcH3) and AcH4. However, the precise modification pattern that it reads and the writer for generating this pattern are unknown. By examining a pool of latently infected proviruses with diverse integration sites, we found that the LTR characteristically has low AcH3 but high AcH4 content...
April 23, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29679637/recent-stimulant-use-and-leukocyte-gene-expression-in-methamphetamine-users-with-treated-hiv-infection
#9
Adam W Carrico, Annesa Flentje, Kord Kober, Sulggi Lee, Peter Hunt, Elise D Riley, Steven Shoptaw, R N Elena Flowers, Samantha E Dilworth, Savita Pahwa, Bradley E Aouizerat
Stimulant use may accelerate HIV disease progression through biological and behavioral pathways. However, scant research with treated HIV-positive persons has examined stimulant-associated alterations in pathophysiologic processes relevant to HIV pathogenesis. In a sample of 55 HIV-positive, methamphetamine-using sexual minority men with a viral load less than 200 copies/mL, we conducted RNA sequencing to examine patterns of leukocyte gene expression in participants who had a urine sample that was reactive for stimulants (n = 27) as compared to those who tested non-reactive (n = 28)...
April 18, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29596334/tackling-hiv-persistence-pharmacological-versus-crispr-based-shock-strategies
#10
REVIEW
Gilles Darcis, Atze T Das, Ben Berkhout
Jan Svoboda studied aspects of viral latency, in particular with respect to disease induction by avian RNA tumor viruses, which were later renamed as part of the extended retrovirus family. The course of retroviral pathogenesis is intrinsically linked to their unique property of integrating the DNA copy of the retroviral genome into that of the host cell, thus forming the provirus. Retroviral latency has recently become of major clinical interest to allow a better understanding of why we can effectively block the human immunodeficiency virus type 1 (HIV-1) in infected individuals with antiviral drugs, yet never reach a cure...
March 29, 2018: Viruses
https://www.readbyqxmd.com/read/29577368/productively-infected-cd4-cells-express-higher-human-telomerase-reverse-transcriptase-levels-indicating-a-possible-mechanism-of-persistence-in-hiv-infection
#11
Poonam Suryawanshi, Sheela Godbole, Jyoti Pawar, Madhuri Thakar, Ashwini Shete
Mechanisms involved in survival of productively infected memory CD4+cells after initial antigenic stimulation and their subsequent reversion to resting state are critical for the development of the predominant replication competent Human Immunodeficiency Virus (HIV) reservoir. These mechanisms might also counter their elimination after HIV reactivation through latency-reversing agents (LRA), making their evaluation critical in devising strategies for HIV eradication using the appropriate HIV latency model recapitulating the predominant replication-competent HIV reservoir...
March 25, 2018: Microbiology and Immunology
https://www.readbyqxmd.com/read/29558453/role-of-pattern-recognition-receptors-in-kshv-infection
#12
REVIEW
Timsy Uppal, Roni Sarkar, Ranjit Dhelaria, Subhash C Verma
Kaposi's sarcoma-associated herpesvirus or Human herpesvirus-8 (KSHV/HHV-8), an oncogenic human herpesvirus and the leading cause of cancer in HIV-infected individuals, is a major public health concern with recurring reports of epidemics on a global level. The early detection of KSHV virus and subsequent activation of the antiviral immune response by the host's immune system are crucial to prevent KSHV infection. The host's immune system is an evolutionary conserved system that provides the most important line of defense against invading microbial pathogens, including viruses...
March 20, 2018: Cancers
https://www.readbyqxmd.com/read/29541372/elimination-of-hiv-1-latently-infected-cells-by-gnidimacrin-and-a-selective-hdac-inhibitor
#13
Li Huang, Wei-Hong Lai, Lei Zhu, Wei Li, Lei Wei, Kuo-Hsiung Lee, Lan Xie, Chin-Ho Chen
We have previously reported gnidimacrin (GM), a protein kinase C (PKC) agonist, significantly reduces the frequency of HIV-1 latently infected cells in peripheral blood mononuclear cells (PBMCs) from patients undergoing successful antiretroviral therapy at low picomolar concentrations ex vivo , which is distinct from other latency reversing agents. In this study, we demonstrate that strong viral reactivation by GM is a mechanism for elimination of latently infected cells, and a histone deacetylase inhibitor (HDACI), a thiophenyl benzamide (TPB), further potentiated the efficacy of GM against latent HIV-1...
March 8, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29520278/interferon-%C3%AE-subtypes-as-an-adjunct-therapeutic-approach-for-human-immunodeficiency-virus-functional-cure
#14
REVIEW
Jeffy George, Joseph J Mattapallil
Human immunodeficiency virus (HIV) establishes life-long latency in infected individuals. Although highly active antiretroviral therapy (HAART) has had a significant impact on the course of HIV infection leading to a better long-term outcome, the pool of latent reservoir remains substantial even under HAART. Numerous approaches have been under development with the goal of eradicating the latent HIV reservoir though with limited success. Approaches that combine immune-mediated control of HIV to activate both the innate and the adaptive immune system under suppressive therapy along with "shock and kill" drugs may lead to a better control of the reactivated virus...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29491165/tunneling-nanotubes-as-a-novel-route-of-cell-to-cell-spread-of-herpesviruses
#15
Mirosława Panasiuk, Michał Rychłowski, Natalia Derewońko, Krystyna Bieńkowska-Szewczyk
Various types of intercellular connections that are essential for communication between cells are often utilized by pathogens. Recently, a new type of cellular connection, consisting of long, thin, actin-rich membrane extensions named tunneling nanotubes (TNTs), has been shown to play an important role in cell-to-cell spread of HIV and influenza virus. In the present report, we show that TNTs are frequently formed by cells infected by an alphaherpesvirus, bovine herpesvirus 1 (BoHV-1). Viral proteins, such as envelope glycoprotein E (gE), capsid protein VP26, and tegument protein Us3, as well as cellular organelles (mitochondria) were detected by immunofluorescence and live-cell imaging of nanotubes formed by bovine primary fibroblasts and oropharynx cells (KOP cells)...
May 15, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29491162/long-noncoding-rna-uc002yug-2-activates-hiv-1-latency-through-regulation-of-mrna-levels-of-various-runx1-isoforms-and-increased-tat-expression
#16
Chen Huan, Zhaolong Li, Shanshan Ning, Hong Wang, Xiao-Fang Yu, Wenyan Zhang
The HIV-1 reservoir is a major obstacle to complete eradication of the virus. Although many proteins and RNAs have been characterized as regulators in HIV-1/AIDS pathogenesis and latency, only a few long noncoding RNAs (lncRNAs) have been shown to be closely associated with HIV-1 replication and latency. In this study, we demonstrated that lncRNA uc002yug.2 plays a key role in HIV-1 replication and latency. uc002yug.2 potentially enhances HIV-1 replication, long terminal repeat (LTR) activity, and the activation of latent HIV-1 in both cell lines and CD4+ T cells from patients...
May 1, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29476067/bi-2536-and-bi-6727-dual-polo-like-kinase-bromodomain-inhibitors-effectively-reactivate-latent-hiv-1
#17
Jin Gohda, Kazuo Suzuki, Kai Liu, Xialin Xie, Hiroaki Takeuchi, Jun-Ichiro Inoue, Yasushi Kawaguchi, Takaomi Ishida
HIV-1 latent reservoirs harbouring silenced but replication-competent proviruses are a major obstacle against viral eradication in infected patients. The "shock and kill" strategy aims to reactivate latent provirus with latency reversing agents (LRAs) in the presence of antiretroviral drugs, necessitating the development of effective and efficient LRAs. We screened a chemical library for potential LRAs and identified two dual Polo-like kinase (PLK)/bromodomain inhibitors, BI-2536 and BI-6727 (volasertib), which are currently undergoing clinical trials against various cancers...
February 23, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29464785/astrocytes-sustain-long-term-productive-hiv-1-infection-without-establishment-of-reactivable-viral-latency
#18
Corinne Barat, Alizé Proust, Alexandre Deshiere, Mathieu Leboeuf, Jean Drouin, Michel J Tremblay
The "shock and kill" HIV-1 cure strategy proposes eradication of stable cellular reservoirs by clinical treatment with latency-reversing agents (LRAs). Although resting CD4+ T cells latently infected with HIV-1 constitute the main reservoir that is targeted by these approaches, their consequences on other reservoirs such as the central nervous system are still unknown and should be taken into consideration. We performed experiments aimed at defining the possible role of astrocytes in HIV-1 persistence in the brain and the effect of LRA treatments on this viral sanctuary...
February 21, 2018: Glia
https://www.readbyqxmd.com/read/29457784/hiv-latency-is-reversed-by-acss2-driven-histone-crotonylation
#19
Guochun Jiang, Don Nguyen, Nancie M Archin, Steven A Yukl, Gema Méndez-Lagares, Yuyang Tang, Maher M Elsheikh, George R Thompson, Dennis J Hartigan-O'Connor, David M Margolis, Joseph K Wong, Satya Dandekar
Eradication of HIV-1 (HIV) is hindered by stable viral reservoirs. Viral latency is epigenetically regulated. While the effects of histone acetylation and methylation at the HIV long-terminal repeat (LTR) have been described, our knowledge of the proviral epigenetic landscape is incomplete. We report that a previously unrecognized epigenetic modification of the HIV LTR, histone crotonylation, is a regulator of HIV latency. Reactivation of latent HIV was achieved following the induction of histone crotonylation through increased expression of the crotonyl-CoA-producing enzyme acyl-CoA synthetase short-chain family member 2 (ACSS2)...
March 1, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29451894/trade-off-between-synergy-and-efficacy-in-combinations-of-hiv-1-latency-reversing-agents
#20
Vipul Gupta, Narendra M Dixit
Eradicating HIV-1 infection is difficult because of the reservoir of latently infected cells that gets established soon after infection, remains hidden from antiretroviral drugs and host immune responses, and retains the capacity to reignite infection following the cessation of treatment. Drugs called latency-reversing agents (LRAs) are being developed to reactivate latently infected cells and render them susceptible to viral cytopathicity or immune killing. Whereas individual LRAs have failed to induce adequate reactivation, pairs of LRAs have been identified recently that act synergistically and hugely increase reactivation levels compared to individual LRAs...
February 2018: PLoS Computational Biology
keyword
keyword
33477
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"