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https://www.readbyqxmd.com/read/29147885/proceedings-of-the-2017-isev-symposium-on-hiv-neurohiv-drug-abuse-evs
#1
Guoku Hu, Sowmya Yelamanchili, Fatah Kashanchi, Norman Haughey, Vincent C Bond, Kenneth W Witwer, Lynn Pulliam, Shilpa Buch
Despite the success of combination antiretroviral therapy (cART), there is increased prevalence of HIV-associated neurocognitive disorders (HAND) in HIV-1-infected individuals on cART, which poses a major health care challenge. Adding further complexity to this long-term antiretroviral use is the comorbidity with drugs of abuse such as morphine, cocaine, and methamphetamine, which can in turn, exacerbate neurologic and cognitive deficits associated with HAND. Furthermore, HIV proteins, such as the transactivator of transcription (Tat) and the envelope protein (gp120), as well as antiretrovirals themselves can also contribute to the progression of neurodegeneration underlying HAND...
November 16, 2017: Journal of Neurovirology
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
#2
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/29140109/host-methyltransferases-and-demethylases-potential-new-epigenetic-targets-for-hiv-cure-strategies-and-beyond
#3
Daniela Boehm, Melanie Ott
A successful HIV cure strategy may require reversing HIV latency to purge hidden viral reservoirs or enhancing HIV latency to permanently silence HIV transcription. Epigenetic modifying agents show promise as antilatency therapeutics in vitro and ex vivo, but also affect other steps in the viral life cycle. In this review, we summarize what we know about cellular DNA and protein methyltransferases (PMTs) as well as demethylases involved in HIV infection. We describe the biology and function of DNA methyltransferases, and their controversial role in HIV infection...
November 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29135580/wake-me-up-before-you-go-a-strategy-to-reduce-the-latent-hiv-reservoir
#4
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/29120617/live-visualization-of-hiv-1-proviral-dna-using-a-dual-color-labeled-crispr-system
#5
Yingxin Ma, Mingxiu Wang, Wei Li, Zhi-Ping Zhang, Xiaowei Zhang, Tianwei Tan, Zongqiang Cui, Xian-En Zhang
HIV latency is one of the major problems in HIV/AIDS cure. Imaging single-copy integrated proviral HIV DNA in host cell has both virology and clinical significance but remains technical challenge. Here, we developed a dual-color labeled CRISPR system to image the HIV-1 integrated proviral DNA in latently infected cells. The pair of CRISPRs was fluorescently labeled with two different color QDs using two alternative bioorthogonal ligation reactions. Integrated HIV-sequences are successfully mapped based on the co-localized signals of QDs in living cells...
November 9, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29118123/estimating-initial-viral-levels-during-hiv-siv-reactivation-from-latency
#6
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/29112072/an-advanced-blt-humanized-mouse-model-for-extended-hiv-1-cure-studies
#7
Kerry J Lavender, Craig Pace, Kathrin Sutter, Ronald J Messer, Dakota L Pouncey, Nathan W Cummins, Sekar Natesampillai, Jim Zheng, Joshua Goldsmith, Marek Widera, Erik S Van Dis, Katie Phillips, Brent Race, Ulf Dittmer, George Kukolj, Kim J Hasenkrug
OBJECTIVE: Although BLT-humanized mice provide a robust model for HIV-1 infection and enable evaluation of cure strategies dependent on endogenous immune responses, most mice develop graft versus host disease (GVHD), limiting their utility for extended HIV cure studies. This study aimed to: 1) Evaluate the GVHD-resistant C57BL/6 Rag2γcCD47 triple knockout (TKO)-BLT mouse as a model to establish HIV-1 latency. 2) Determine whether TKO-BLT mice could be maintained on ART for extended periods of time...
November 2, 2017: AIDS
https://www.readbyqxmd.com/read/29099677/novel-latency-reversal-agents-for-hiv-1-cure
#8
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/29098230/rna-mediated-tilda-for-improved-cell-capacity-and-enhanced-detection-of-multiply-spliced-hiv-rna
#9
Hannah M Pezzi, Scott M Berry, David J Beebe, Rob Striker
Quantification of the HIV viral reservoir is critical to understanding HIV latency, advancing patient care and ultimately achieving a cure. To quantify the reservoir, a new metric was recently introduced, which quantified cells carrying multiply spliced HIV RNA. The developed assay, Tat/rev Induced Limiting Dilution Assay (TILDA), enables quantification of cells containing multiply-spliced HIV RNA events as an indicator of reservoir size. Due to TILDA's reliance on a limiting dilution format paired with the rarity of target events, numerous individual reactions are required to obtain a single endpoint...
November 13, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/29089933/curaxin-cbl0100-blocks-hiv-1-replication-and-reactivation-through-inhibition-of-viral-transcriptional-elongation
#10
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/29082287/flow-cytometric-analysis-of-hiv-1-transcriptional-activity-in-response-to-shrna-knockdown-in-a2-and-a72-j-lat-cell-lines
#11
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). To eliminate viral reservoirs, one strategy focuses on reversing HIV-1 latency via 'shock and kill' (Deeks, 2012). The basis of this strategy is to overcome the molecular mechanisms of HIV-1 latency by therapeutically inducing viral gene and protein expression under antiretroviral therapy and to cause selective cell death via the lytic properties of the virus, or the immune system now recognizing the infected cells...
June 5, 2017: Bio-protocol
https://www.readbyqxmd.com/read/29071475/assays-to-measure-latency-reservoirs-and-reactivation
#12
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/29071474/molecular-control-of-hiv-and-siv-latency
#13
Gilles Darcis, Benoit Van Driessche, Sophie Bouchat, Frank Kirchhoff, Carine Van Lint
The HIV latent reservoirs are considered as the main hurdle to viral eradication. Numerous mechanisms lead to the establishment of HIV latency and act at the transcriptional and post-transcriptional levels. A better understanding of latency is needed in order to ultimately achieve a cure for HIV. The mechanisms underlying latency vary between patients, tissues, anatomical compartments, and cell types. From this point of view, simian immunodeficiency virus (SIV) infection and the use of nonhuman primate (NHP) models that recapitulate many aspects of HIV-associated latency establishment and disease progression are essential tools since they allow extensive tissue sampling as well as a control of infection parameters (virus type, dose, route, and time)...
October 26, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/29071045/repeated-spontaneous-clearance-of-hepatitis-c-virus-infection-in-the-setting-of-long-term-non-progression-of-hiv-infection
#14
Genevieve Kerkerian, Arshia Alimohammadi, Tyler Raycraft, Brian Conway
Hepatitis C Virus (HCV) and human immunodeficiency virus (HIV) are global pandemics that affect 170 million and 35 million individuals, respectively. Up to 45% of individuals infected with HCV clear their infections spontaneously - correlating to factors like aboriginal descent and some host specific immune factors. HIV, however, establishes true latency in infected cells and cannot be cured. In the setting of longterm non-progressors (LTNPs) of HIV, a state of immune preservation and low circulating viral load is established...
October 2, 2017: Infectious Disease Reports
https://www.readbyqxmd.com/read/29057080/the-role-of-mir-29a-in-hiv-1-replication-and-latency
#15
EDITORIAL
Giacomo Frattari, Lars Aagaard, Paul W Denton
The development of an effective HIV-1 eradication strategy relies upon a clear understanding of the cellular mechanisms involved in HIV-1 latency. Among such cellular processes, microRNA activities affect HIV-1 production by regulating viral transcripts as well as host cell HIV-1 dependency factors. miR-29a stands apart from other relevant microRNAs as a potential therapeutic target in HIV-1 eradication. In vitro experiments have shown that miR-29a binds to a sequence in the 3'UTR of viral transcripts and inhibits their expression...
October 1, 2017: Journal of Virus Eradication
https://www.readbyqxmd.com/read/29046460/myeloid-dendritic-cells-repress-human-cytomegalovirus-gene-expression-and-spread-by-releasing-interferon-unrelated-soluble-antiviral-factors
#16
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/29045905/transcriptional-reprogramming-during-effector-to-memory-transition-renders-cd4-t-cells-permissive-for-latent-hiv-1-infection
#17
Liang Shan, Kai Deng, Hongbo Gao, Sifei Xing, Adam A Capoferri, Christine M Durand, S Alireza Rabi, Gregory M Laird, Michelle Kim, Nina N Hosmane, Hung-Chih Yang, Hao Zhang, Joseph B Margolick, Linghua Li, Weiping Cai, Ruian Ke, Richard A Flavell, Janet D Siliciano, Robert F Siliciano
The latent reservoir for HIV-1 in resting memory CD4(+) T cells is the major barrier to curing HIV-1 infection. Studies of HIV-1 latency have focused on regulation of viral gene expression in cells in which latent infection is established. However, it remains unclear how infection initially becomes latent. Here we described a unique set of properties of CD4(+) T cells undergoing effector-to-memory transition including temporary upregulation of CCR5 expression and rapid downregulation of cellular gene transcription...
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29045893/hiv-1-latency-by-transition
#18
Boris Julg, Dan H Barouch
The latent HIV-1 reservoir represents the major barrier for the development of an HIV-1 cure. In this issue of Immunity, Shan et al. (2017) highlight that effector-to-memory transitioning (EMT) CD4(+) T cells are particularly permissive for the establishment of latent HIV-1 infection.
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29045830/in%C3%A2-vivo-suppression-of-hiv-rebound-by-didehydro-cortistatin-a-a-block-and-lock-strategy-for-hiv-1-treatment
#19
Cari F Kessing, Christopher C Nixon, Chuan Li, Perry Tsai, Hiroshi Takata, Guillaume Mousseau, Phong T Ho, Jenna B Honeycutt, Mohammad Fallahi, Lydie Trautmann, J Victor Garcia, Susana T Valente
HIV-1 Tat activates viral transcription and limited Tat transactivation correlates with latency establishment. We postulated a "block-and-lock" functional cure approach based on properties of the Tat inhibitor didehydro-Cortistatin A (dCA). HIV-1 transcriptional inhibitors could block ongoing viremia during antiretroviral therapy (ART), locking the HIV promoter in persistent latency. We investigated this hypothesis in human CD4(+) T cells isolated from aviremic individuals. Combining dCA with ART accelerates HIV-1 suppression and prevents viral rebound after treatment interruption, even during strong cellular activation...
October 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/29045398/nonlatching-positive-feedback-enables-robust-bimodality-by-decoupling-expression-noise-from-the-mean
#20
Brandon S Razooky, Youfang Cao, Maike M K Hansen, Alan S Perelson, Michael L Simpson, Leor S Weinberger
Fundamental to biological decision-making is the ability to generate bimodal expression patterns where 2 alternate expression states simultaneously exist. Here, we use a combination of single-cell analysis and mathematical modeling to examine the sources of bimodality in the transcriptional program controlling HIV's fate decision between active replication and viral latency. We find that the HIV transactivator of transcription (Tat) protein manipulates the intrinsic toggling of HIV's promoter, the long terminal repeat (LTR), to generate bimodal ON-OFF expression and that transcriptional positive feedback from Tat shifts and expands the regime of LTR bimodality...
October 2017: PLoS Biology
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