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https://www.readbyqxmd.com/read/28641539/role-of-host-factors-on-the-regulation-of-tat-mediated-hiv-1-transcription
#1
Guillaume Mousseau, Susana T Valente
BACKGROUND: The viral transactivator Tat protein is a key modulator of HIV-1 replication, as it regulates transcriptional elongation from the integrated proviral genome. Tat recruits the human transcription elongation factor b, and other host proteins, such as the super elongation complex, to activate the cellular RNA polymerase II, normally stalled shortly after transcription initiation at the HIV promoter. By means of a complex set of interactions with host cellular factors, Tat determines the fate of viral activity within the infected cell...
June 22, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28641535/hiv-1-transcription-inhibitors-increase-the-synthesis-of-viral-non-coding-rna-that-contribute-to-latency
#2
Yao A Akpamagbo, Catherine DeMarino, Michelle L Pleet, Angela Schwab, Myosotys Rodriguez, Robert A Barclay, Gavin Sampey, Sergey Iordanskiy, Nazira El-Hage, Fatah Kashanchi
BACKGROUND: HIV-1 can be preserved in long-lived resting CD4+ T- and myeloid cells, forming a viral reservoir in tissues of the infected individuals. Infected patients primarily receive cART, which, to date, is the most efficient treatment against HIV/AIDS. However, the major problem in the eradication of HIV-1 from patients is the lack of therapeutic approaches to recognize the latent HIV-1 provirus and to eliminate latently infected cells. RESULTS: In the current review, we describe the effect of HIV-1 transcriptional inhibitors CR8#13 and F07#13 using a series of in vitro and in vivo assays...
June 22, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28640909/hiv-tat-regulates-macrophage-gene-expression-in-the-context-of-neuroaids
#3
Loreto Carvallo, Lillie Lopez, Jorge E Fajardo, Matias Jaureguiberry-Bravo, Andras Fiser, Joan W Berman
Despite the success of cART, greater than 50% of HIV infected people develop cognitive and motor deficits termed HIV-associated neurocognitive disorders (HAND). Macrophages are the major cell type infected in the CNS. Unlike for T cells, the virus does not kill macrophages and these long-lived cells may become HIV reservoirs in the brain. They produce cytokines/chemokines and viral proteins that promote inflammation and neuronal damage, playing a key role in HIV neuropathogenesis. HIV Tat is the transactivator of transcription that is essential for replication and transcriptional regulation of the virus and is the first protein to be produced after HIV infection...
2017: PloS One
https://www.readbyqxmd.com/read/28639194/rnaa-induced-by-tata-box-targeting-micrornas
#4
Yijun Zhang, Hui Zhang
Recent studies reveal that some nuclear microRNAs (miRNA) and synthesized siRNAs target gene promoters to activate gene transcription (RNAa). Interestingly, our group identified a novel HIV-1-encoded miRNA, miR-H3, which targets specifically the core promoter TATA box of HIV-1 and activates viral gene expression. Depletion of miR-H3 significantly impaired the replication of HIV-1. miR-H3 mimics could activate viruses from CD4(+) T cells isolated from patients receiving suppressive highly active antiretroviral therapy, which is very intriguing for reducing HIV-1 latent reservoir...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28638377/a-novel-bromodomain-inhibitor-reverses-hiv-1-latency-through-specific-binding-with-brd4-to-promote-tat-and-p-tefb-association
#5
Huachao Huang, Shuai Liu, Maxime Jean, Sydney Simpson, He Huang, Mark Merkley, Tsuyoshi Hayashi, Weili Kong, Irene Rodríguez-Sánchez, Xiaofeng Zhang, Hailemichael O Yosief, Hongyu Miao, Jianwen Que, James J Kobie, James Bradner, Netty G Santoso, Wei Zhang, Jian Zhu
While combinatory antiretroviral therapy (cART) can effectively reduce HIV-1 viremia, it cannot eliminate HIV-1 infection. In the presence of cART, viral reservoirs remain latent, impeding the cure of HIV-1/AIDS. Recently, latency-reversing agents (LRAs) have been developed with the intent of purging latent HIV-1, providing an intriguing strategy for the eradication of the residual viral reservoirs. Our earlier studies show that the first-generation, methyl-triazolo bromodomain, and extra-terminal domain inhibitor (BETi), JQ1, facilitates the reversal of HIV-1 latency...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28638104/anti-proliferative-therapy-for-hiv-cure-a-compound-interest-approach
#6
Daniel B Reeves, Elizabeth R Duke, Sean M Hughes, Martin Prlic, Florian Hladik, Joshua T Schiffer
In the era of antiretroviral therapy (ART), HIV-1 infection is no longer tantamount to early death. Yet the benefits of treatment are available only to those who can access, afford, and tolerate taking daily pills. True cure is challenged by HIV latency, the ability of chromosomally integrated virus to persist within memory CD4(+) T cells in a non-replicative state and activate when ART is discontinued. Using a mathematical model of HIV dynamics, we demonstrate that treatment strategies offering modest but continual enhancement of reservoir clearance rates result in faster cure than abrupt, one-time reductions in reservoir size...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28630490/pyroptosis-superinfection-and-the-maintenance-of-the-latent-reservoir-in-hiv-1-infection
#7
Dominik Wodarz, David N Levy
A long-lived reservoir of latently infected T cells prevents antiretroviral therapy from eliminating HIV-1 infection. Furthering our understanding of the dynamics of latency generation and maintenance is therefore vital to improve treatment outcome. Using mathematical models and experiments, we suggest that the death of latently infected cells brought about by pyroptosis, or to a lesser extent by superinfection, might be key mechanisms to account for the size and composition of the latent reservoir. Pyroptosis is a form of cell death that occurs in a resting (and thus latently infected) T cell when a productively infected cell attempts cell-to-cell transmission of virus...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28628632/increasing-procaspase-8-expression-using-repurposed-drugs-to-induce-hiv-infected-cell-death-in-ex-vivo-patient-cells
#8
Rahul Sampath, Nathan W Cummins, Sekar Natesampillai, Gary D Bren, Thomas D Chung, Jason Baker, Keith Henry, Amélie Pagliuzza, Andrew D Badley
HIV persists because a reservoir of latently infected CD4 T cells do not express viral proteins and are indistinguishable from uninfected cells. One approach to HIV cure suggests that reactivating HIV will activate cytotoxic pathways; yet when tested in vivo, reactivating cells do not die sufficiently to reduce cell-associated HIV DNA levels. We recently showed that following reactivation from latency, HIV infected cells generate the HIV specific cytotoxic protein Casp8p41 which is produced by HIV protease cleaving procaspase 8...
2017: PloS One
https://www.readbyqxmd.com/read/28628526/determinants-of-hiv-1-cd4-independent-brain-adaptation
#9
Madina Shakirzyanova, Xiang-Peng Kong, Cecilia Cheng-Mayer
BACKGROUND: HIV-1 is known to adapt to the local environment in its usage of receptors and it can become CD4 independent in the brain where the receptor is scarce. This adaptation is through amino acid variations, but the patterns of such variation are not yet well understood. Given that infection of long-lived CD4-low and CD4-negative cells in anatomic compartments such as the brain expand cell tropism in vivo and may serve as potential viral reservoirs that pose challenge for HIV eradication, understanding the evolution to CD4-independence and envelope conformation associated with infection in the absence of CD4 will not only broaden our insights into HIV pathogenesis, but may guide functional cure strategies as well...
June 15, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28628041/hiv-persistence-clonal-expansion-of-cells-in-the-latent-reservoir
#10
Kyungyoon J Kwon, Robert F Siliciano
While antiretroviral therapy (ART) can reduce HIV-1 to undetectable levels, the virus generally reappears if treatment is stopped. Resurgence of the virus is due to the reactivation of T cells harboring latent integrated provirus, and recent studies indicate that proliferation of these latently infected cells helps maintain the HIV-1 reservoir. In this issue of the JCI, Lee et al. evaluated CD4+ T cell subsets to determine whether certain populations are more likely to harbor full-length, replication-competent provirus...
June 19, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28625133/recent-advances-in-targeting-the-hiv-1-tat-tar-complex
#11
Fardokht A Abulwerdi, Stuart F J Le Grice
Following seminal discoveries by Rosen and co-workers in 1985, the HIV-1 TAR has emerged as one of the most extensively studied regulatory elements of the HIV-1 genome. Located adjacent to the long terminal repeat promoter, this cis-acting motif, in conjunction with the viral Tat protein, plays a critical role in viral genomic RNA synthesis via modification of the transcription complex. As such, the Tat/TAR axis has been the subject of intense efforts aimed at developing therapeutic interventions, directed against both the protein and nucleic acid components...
June 15, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28620380/human-immunodeficiency-virus-playing-hide-and-seek-understanding-the-tfh-cell-reservoir-and-proposing-strategies-to-overcome-the-follicle-sanctuary
#12
REVIEW
Yew Ann Leong, Anurag Atnerkar, Di Yu
Human immunodeficiency virus (HIV) infects millions of people worldwide, and new cases continue to emerge. Once infected, the virus cannot be cleared by the immune system and causes acquired immunodeficiency syndrome. Combination antiretroviral therapeutic regimen effectively suppresses viral replication and halts disease progression. The treatment, however, does not eliminate the virus-infected cells, and interruption of treatment inevitably leads to viral rebound. The rebound virus originates from a group of virus-infected cells referred to as the cellular reservoir of HIV...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28617961/interlaboratory-quality-control-of-total-hiv-1-dna-load-measurement-for-multicenter-reservoir-studies
#13
Pierre Gantner, Adeline Mélard, Florence Damond, Constance Delaugerre, Julia Dina, Marie Gueudin, Anne Maillard, Karine Sauné, Audrey Rodallec, Edouard Tuaillon, Jean-Christophe Plantier, Christine Rouzioux, Véronique Avettand-Fenoel
BACKGROUND: Viral reservoirs represent an important barrier to HIV cure. Accurate markers of HIV reservoirs are needed to develop multicenter studies. The aim of this multicenter quality control (QC) was to evaluate the inter-laboratory reproducibility of total HIV-1-DNA quantification. METHODS: Ten laboratories of the ANRS-AC11 working group participated by quantifying HIV-DNA with a real-time qPCR assay (Biocentric) in 4 samples (QCMD). RESULTS: Good reproducibility was found between laboratories (standard deviation ≤ 0...
June 15, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28609403/early-antiretroviral-therapy-reduces-hiv-dna-following-perinatal-hiv-infection
#14
Caroline Foster, Matthew Pace, Steve Kaye, Emily Hopkins, Mathew Jones, Nicola Robinson, Sarah Fidler, John Frater
: The impact of antiretroviral therapy (ART) on the size of the HIV reservoir has implications for virological remission in adults, but is not well characterised in perinatally acquired infection (PaHIV). In a prospective observational study of 20 children with PaHIV and sustained viral suppression on ART for >5 years, proviral DNA was significantly higher in deferred (>4 years) versus early (first year of life) ART recipients (p = 0.0062), and correlated with age of initiation (p = 0.13; r = 0...
June 12, 2017: AIDS
https://www.readbyqxmd.com/read/28605173/barriers-to-hiv-remission-research-in-low-and-middle-income-countries
#15
REVIEW
Theresa Rossouw, Joseph D Tucker, Gert U van Zyl, Kenly Sikwesi, Catherine Godfrey
INTRODUCTION: HIV eradication and remission research has largely taken place in high-income countries. In low- and middle-income countries (LMIC), there may be factors that have a substantial impact on the size of the latent HIV reservoir and the immunological response to infection. If a curative strategy is to be available to all HIV-infected individuals, these factors must be understood. METHODS: We use a scoping review to examine the literature on biological factors that may have an impact on HIV persistence in LMIC...
June 5, 2017: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/28603436/reduced-adherence-to-antiretroviral-therapy-is-associated-with-residual-low-level-viremia
#16
Franco Maggiolo, Elisa Di Filippo, Laura Comi, Annapaola Callegaro, Giorgio L Colombo, Sergio Di Matteo, Daniela Valsecchi, Marco Rizzi
The source and significance of residual low-level viremia (LLV) during combinational antiretroviral therapy (cART) remain a matter of controversy. It is unclear whether residual viremia depends on ongoing release of HIV from the latent reservoir or if viral replication contributes to LLV. We examined the relationship between adherence and LLV. Adherence was estimated by pharmacy refill and dichotomized as ≥95% or <95%. Plasma HIV-RNA was determined, with an ultrasensitive test having a limit of detection of 3 copies/mL at least 2 times over the follow-up period...
2017: Pragmatic and Observational Research
https://www.readbyqxmd.com/read/28598791/croi-2017-neurologic-complications-of-hiv-infection
#17
Serena S Spudich, Beau M Ances
The brain is a major target for HIV infection and is a potential viral reservoir even in virologically well-controlled HIV-infected individuals. Data presented at the 2017 Conference on Retroviruses and Opportunistic Infections (CROI) suggested that during early HIV infection, CD4+ T cells in the meninges and choroid plexus serve as an important early site of HIV infection in the central nervous system (CNS), with brain macrophages and microglial cells becoming an important source of viral replication with advancing disease...
May 2017: Topics in Antiviral Medicine
https://www.readbyqxmd.com/read/28598788/croi-2017-basic-science-review
#18
Mario Stevenson
The Conference on Retroviruses and Opportunistic Infections (CROI) continues to be the preeminent gathering for HIV/AIDS researchers. It provides a forum in which investigators involved in all aspects of research on HIV/AIDS and related conditions can present and be updated on the latest scientific developments in the field. In 2017, basic research continued to be strongly represented at the conference. Most of the presentations focused on mechanisms of viral persistence in the face of effective antiretroviral therapy as well as approaches to measuring viral reservoirs and intervening in those reservoirs...
May 2017: Topics in Antiviral Medicine
https://www.readbyqxmd.com/read/28592538/identification-of-il-27-il-27ra-as-a-critical-immune-axis-for-in-vivo-hiv-control
#19
M Ruiz-Riol, D Berdnik, A Llano, B Mothe, C Gálvez, S Pérez-Álvarez, B Oriol-Tordera, A Olvera, S Silva-Arrieta, Michael Meulbroek, Ferran Pujol, J Coll, J Martinez-Picado, C Ganoza, J Sanchez, G Gómez, T Wyss-Coray, C Brander
Intact and broad immune cell effector functions and specific individual cytokines have been linked to HIV disease outcome, but their relative contribution to HIV control remains unclear. We asked whether the proteome of secreted cytokines and signaling factors in peripheral blood can be used to discover specific pathways critical for host viral control. A custom glass-based microarray able to measure >600 plasma proteins involved in cell-to-cell communication was used to measure plasma protein profiles in 96 HIV-infected, treatment-naïve individuals with high (>50,000) or low (<10,000 HIV RNA copies/ml) viral loads...
June 7, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28592534/comprehensive-cross-clade-characterization-of-antibody-mediated-recognition-complement-mediated-lysis-and-cell-mediated-cytotoxicity-of-hiv-1-envelope-specific-antibodies-towards-the-eradication-of-the-hiv-1-reservoir
#20
Shariq Mujib, Jun Liu, A K M Nur-Ur Rahman, Jordan A Schwartz, Phil Bonner, Feng Yun Yue, Mario A Ostrowski
Immunotherapy with passive administration of broadly neutralizing HIV-1 envelope-specific antibodies (bnAbs) in the setting of established infection in vivo has yielded mixed results. The contribution of different antibodies toward the direct elimination of infected cells is poorly understood. Here, we determined the ability of twelve well-characterized anti-HIV-1 neutralizing antibodies to recognize and eliminate primary CD4 T cells infected with HIV-1, belonging to clades A, B, C and D, via antibody-dependent complement-mediated lysis (ADCML) and antibody-dependent cell-mediated cytotoxicity (ADCC), in vitro...
June 7, 2017: Journal of Virology
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