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Latent hiv reservoir

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https://www.readbyqxmd.com/read/29140108/cytomegalovirus-and-hiv-persistence-pouring-gas-on-the-fire
#1
Aaron Christensen-Quick, Christophe Vanpouille, Andrea Lisco, Sara Gianella
The inherent stability of a small population of T cells that are latently infected with HIV despite antiretroviral therapy (ART) remains a stubborn obstacle to an HIV cure. By exploiting the memory compartment of our immune system, HIV maintains persistence in a small subset of quiescent cells with varying phenotypes, thus evading immune surveillance and clinical detection. Understanding the molecular and immunological mechanisms that maintain the latent reservoir will be critical to the success of HIV eradication strategies...
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
#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/29126877/chidamide-a-histone-deacetylase-inhibitor-based-anticancer-drug-effectively-reactivates-latent-hiv-1-provirus
#3
Wenqian Yang, Zhiwu Sun, Chen Hua, Qian Wang, Wei Xu, Qiwen Deng, Yanbin Pan, Lu Lu, Shibo Jiang
Although combination antiretroviral therapy (cART) is highly effective in suppressing human immunodeficiency virus type 1 (HIV-1) replication, it fails to eradicate the virus from HIV-1-infected individuals because HIV-1 integrates into the resting CD4(+) T cells, establishing latently infected reservoirs. Histone deacetylation is a key element in regulating HIV-1 latent infection. Chidamide, a new anticancer drug, is a novel type of selective histone deacetylase inhibitor. Here we showed that chidamide effectively reactivated HIV-1 latent provirus in different latently infected cell lines in a dose- and time-dependent manner...
November 8, 2017: Microbes and Infection
https://www.readbyqxmd.com/read/29119608/synthetic-aav-crispr-vectors-for-blocking-hiv-1-expression-in-persistently-infected-astrocytes
#4
Christine Kunze, Kathleen Börner, Eike Kienle, Tanja Orschmann, Ejona Rusha, Martha Schneider, Milena Radivojkov-Blagojevic, Micha Drukker, Sabrina Desbordes, Dirk Grimm, Ruth Brack-Werner
Astrocytes, the most abundant cells in the mammalian brain, perform key functions and are involved in several neurodegenerative diseases. The human immunodeficiency virus (HIV) can persist in astrocytes, contributing to the HIV burden and neurological dysfunctions in infected individuals. While a comprehensive approach to HIV cure must include the targeting of HIV-1 in astrocytes, dedicated tools for this purpose are still lacking. Here we report a novel Adeno-associated virus-based vector (AAV9P1) with a synthetic surface peptide for transduction of astrocytes...
November 9, 2017: Glia
https://www.readbyqxmd.com/read/29112956/hiv-1-persistence-following-extremely-early-initiation-of-antiretroviral-therapy-art-during-acute-hiv-1-infection-an-observational-study
#5
Timothy J Henrich, Hiroyu Hatano, Oliver Bacon, Louise E Hogan, Rachel Rutishauser, Alison Hill, Mary F Kearney, Elizabeth M Anderson, Susan P Buchbinder, Stephanie E Cohen, Mohamed Abdel-Mohsen, Christopher W Pohlmeyer, Remi Fromentin, Rebecca Hoh, Albert Y Liu, Joseph M McCune, Jonathan Spindler, Kelly Metcalf-Pate, Kristen S Hobbs, Cassandra Thanh, Erica A Gibson, Daniel R Kuritzkes, Robert F Siliciano, Richard W Price, Douglas D Richman, Nicolas Chomont, Janet D Siliciano, John W Mellors, Steven A Yukl, Joel N Blankson, Teri Liegler, Steven G Deeks
BACKGROUND: It is unknown if extremely early initiation of antiretroviral therapy (ART) may lead to long-term ART-free HIV remission or cure. As a result, we studied 2 individuals recruited from a pre-exposure prophylaxis (PrEP) program who started prophylactic ART an estimated 10 days (Participant A; 54-year-old male) and 12 days (Participant B; 31-year-old male) after infection with peak plasma HIV RNA of 220 copies/mL and 3,343 copies/mL, respectively. Extensive testing of blood and tissue for HIV persistence was performed, and PrEP Participant A underwent analytical treatment interruption (ATI) following 32 weeks of continuous ART...
November 2017: PLoS Medicine
https://www.readbyqxmd.com/read/29112072/an-advanced-blt-humanized-mouse-model-for-extended-hiv-1-cure-studies
#6
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
#7
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
#8
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
#9
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/29071476/the-antiviral-immune-response-and-its-impact-on-the-hiv-1-reservoir
#10
Rebecca T Veenhuis, Joel N Blankson
Latently infected resting memory CD4(+) T cells represent a major barrier to HIV-1 eradication. Studies have shown that it will not be possible to cure HIV-1 infection unless these cells are eliminated. Latently infected cells probably do not express viral antigens and thus may not be susceptible to the HIV-1 specific immune response, nevertheless the size and composition of the reservoir is influenced by the immune system. In this chapter, we review the different components of the HIV-1 specific immune response and discuss how the immune system can be harnessed to eradicate the virus...
October 26, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/29071475/assays-to-measure-latency-reservoirs-and-reactivation
#11
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
#12
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/29071472/immune-interventions-to-eliminate-the-hiv-reservoir
#13
Denise C Hsu, Jintanat Ananworanich
Inducing HIV remission is a monumental challenge. A potential strategy is the "kick and kill" approach where latently infected cells are first activated to express viral proteins and then eliminated through cytopathic effects of HIV or immune-mediated killing. However, pre-existing immune responses to HIV cannot eradicate HIV infection due to the presence of escape variants, inadequate magnitude, and breadth of responses as well as immune exhaustion. The two major approaches to boost immune-mediated elimination of infected cells include enhancing cytotoxic T lymphocyte mediated killing and harnessing antibodies to eliminate HIV...
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
#14
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/29045906/ctla-4-pd-1-memory-cd4-t-cells-critically-contribute-to-viral-persistence-in-antiretroviral-therapy-suppressed-siv-infected-rhesus-macaques
#15
Colleen S McGary, Claire Deleage, Justin Harper, Luca Micci, Susan P Ribeiro, Sara Paganini, Leticia Kuri-Cervantes, Clarisse Benne, Emily S Ryan, Robert Balderas, Sherrie Jean, Kirk Easley, Vincent Marconi, Guido Silvestri, Jacob D Estes, Rafick-Pierre Sekaly, Mirko Paiardini
Antiretroviral therapy (ART) suppresses viral replication in HIV-infected individuals but does not eliminate the reservoir of latently infected cells. Recent work identified PD-1(+) follicular helper T (Tfh) cells as an important cellular compartment for viral persistence. Here, using ART-treated, SIV-infected rhesus macaques, we show that CTLA-4(+)PD-1(-) memory CD4(+) T cells, which share phenotypic markers with regulatory T cells, were enriched in SIV DNA in blood, lymph nodes (LN), spleen, and gut, and contained replication-competent and infectious virus...
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29045905/transcriptional-reprogramming-during-effector-to-memory-transition-renders-cd4-t-cells-permissive-for-latent-hiv-1-infection
#16
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
#17
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/29045846/identification-of-genetically-intact-hiv-1-proviruses-in-specific-cd4-t-cells-from-effectively-treated-participants
#18
Bonnie Hiener, Bethany A Horsburgh, John-Sebastian Eden, Kirston Barton, Timothy E Schlub, Eunok Lee, Susanne von Stockenstrom, Lina Odevall, Jeffrey M Milush, Teri Liegler, Elizabeth Sinclair, Rebecca Hoh, Eli A Boritz, Daniel Douek, Rémi Fromentin, Nicolas Chomont, Steven G Deeks, Frederick M Hecht, Sarah Palmer
Latent replication-competent HIV-1 persists in individuals on long-term antiretroviral therapy (ART). We developed the Full-Length Individual Proviral Sequencing (FLIPS) assay to determine the distribution of latent replication-competent HIV-1 within memory CD4(+) T cell subsets in six individuals on long-term ART. FLIPS is an efficient, high-throughput assay that amplifies and sequences near full-length (∼9 kb) HIV-1 proviral genomes and determines potential replication competency through genetic characterization...
October 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/29027985/triterpenoids-from-ocimum-labiatum-activates-latent-hiv-1-expression-in-vitro-potential-for-use-in-adjuvant-therapy
#19
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/29021399/modelling-of-anti-latency-treatment-in-hiv-what-is-the-optimal-duration-of-anti-retroviral-free-hiv-remission
#20
Deborah Cromer, Mykola Pinkevych, Thomas A Rasmussen, Sharon R Lewin, Stephen J Kent, Miles P Davenport
A number of treatment strategies are currently being developed to promote anti-retroviral free HIV cure or remission. While complete elimination of the HIV reservoir would prevent recurrence of infection, it is not clear how different remission lengths would affect viral rebound and transmission. In this work we use a stochastic model to show that a treatment that achieves a one-year average time to viral remission will still lead to nearly a quarter of subjects experiencing viral rebound within the first three months...
October 11, 2017: Journal of Virology
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