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https://www.readbyqxmd.com/read/28340355/the-human-immunodeficiency-virus-1-asp-rna-promotes-viral-latency-by-recruiting-the-polycomb-repressor-complex-2-and-promoting-nucleosome-assembly
#1
Juan C Zapata, Federica Campilongo, Robert A Barclay, Catherine DeMarino, Maria D Iglesias-Ussel, Fatah Kashanchi, Fabio Romerio
Various epigenetic marks at the HIV-1 5'LTR suppress proviral expression and promote latency. Cellular antisense transcripts known as long noncoding RNAs (lncRNAs) recruit the polycomb repressor complex 2 (PRC2) to gene promoters, which catalyzes trimethylation of lysine 27 on histone H3 (H3K27me3), thus promoting nucleosome assembly and suppressing gene expression. We found that an HIV-1 antisense transcript expressed from the 3'LTR and encoding the antisense protein ASP promotes proviral latency. Expression of ASP RNA reduced HIV-1 replication in Jurkat cells...
March 21, 2017: Virology
https://www.readbyqxmd.com/read/28329286/short-course-tlr9-agonist-treatment-impacts-innate-immunity-and-plasma-viremia-in-individuals-with-hiv-infection
#2
Line Vibholm, Mariane H Schleimann, Jesper F Højen, Thomas Benfield, Rasmus Offersen, Katrine Rasmussen, Rikke Olesen, Anders Dige, Jørgen Agnholt, Judith Grau, Maria Buzon, Burghardt Wittig, Mathias Lichterfeld, Andreas Munk Petersen, Xutao Deng, Mohammed Abdel-Mohsen, Satish K Pillai, Sofie Rutsaert, Wim Trypsteen, Ward De Spiegelaere, Linos Vandekerchove, Lars Østergaard, Thomas A Rasmussen, Paul W Denton, Martin Tolstrup, Ole S Søgaard
Background: Treatment with latency reversing agents (LRA) enhances HIV-1 transcription in vivo but only leads to modest reductions in the size of the reservoir, possibly due to insufficient immune-mediated elimination of infected cells. We hypothesized that a single drug molecule - a novel toll-like receptor 9 (TLR9) agonist, MGN1703 - could function as an enhancer of innate immunity and an LRA in vivo. Methods: We conducted a single-arm, open-label study, where 15 virologically suppressed HIV-1 infected individuals on antiretroviral therapy received 60 mg MGN1703 s...
March 9, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28324233/diagnosis-and-treatment-of-kaposi-sarcoma
#3
REVIEW
Johann W Schneider, Dirk P Dittmer
Kaposi sarcoma (KS) is the most common neoplasm of people living with HIV today. In Sub-Saharan Africa, KS is among the most common cancers in men, overall. Not only HIV-positive individuals present with KS; any immune compromised person infected with KS-associated herpesvirus (KSHV) or human herpesvirus 8 is at risk: the elderly, children in KSHV-endemic areas, and transplant recipients. KS diagnosis is based on detection of the viral protein latency-associated nuclear antigen (LANA) in the biopsy, but not all cases of KS are the same or will respond to the same therapy...
March 21, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28303346/high-throughput-sequencing-identifies-hiv-1-replication-and-latency-related-mirnas-in-cd4-t-cell-lines
#4
Xiangyun Lu, Jin Yang, Haibo Wu, Zongxing Yang, Changzhong Jin, Juan Wang, Linfang Cheng, Xiaorong Peng, Fumin Liu, Xiuming Peng, Sujing Ji, Huilin Ou, Tiansheng Xie, Hangping Yao, Nanping Wu
MicroRNAs are potent gene expression regulators involved in regulating various biological processes, including host-pathogen interactions. In this study, we used high-throughput sequencing to investigate cellular miRNA signatures related to HIV-1 replication and latent infection in CD4(+) T cell lines, which included HIV-1-replicating H9/HTLV-IIIB, HIV-1-latently-infected CEM-Bru cells, and their parental uninfected H9 and CEM-SS cells. Relatively few miRNAs were found to be modulated by HIV-1 replication or latent infection, while the cell-lineage-specific miRNA difference was more pronounced, irrespective of HIV-1 infection...
March 16, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28279181/a-mature-macrophage-is-a-principal-hiv-1-cellular-reservoir-in-humanized-mice-after-treatment-with-long-acting-antiretroviral-therapy
#5
Mariluz Araínga, Benson Edagwa, R Lee Mosley, Larisa Y Poluektova, Santhi Gorantla, Howard E Gendelman
BACKGROUND: Despite improved clinical outcomes seen following antiretroviral therapy (ART), resting CD4+ T cells continue to harbor latent human immunodeficiency virus type one (HIV-1). However, such cells are not likely the solitary viral reservoir and as such defining where and how others harbor virus is imperative for eradication measures. To such ends, we used HIV-1ADA-infected NOD.Cg-Prkdc (scid) Il2rg (tm1Wjl) /SzJ mice reconstituted with a human immune system to explore two long-acting ART regimens investigating their abilities to affect viral cell infection and latency...
March 9, 2017: Retrovirology
https://www.readbyqxmd.com/read/28275460/reactivation-of-hiv-1-proviruses-in-immune-compromised-mice-engrafted-with-human-voa-negative-cd4-t-cells
#6
EDITORIAL
Zhe Yuan, Guobin Kang, Wuxun Lu, Qingsheng Li
BACKGROUND: HIV-1 infection remains incurable on antiretroviral therapy (ART) due to virus latency. To date, enhanced co-culture assays, including viral outgrowth assays (VOA), are commonly used to measure HIV-1 latent reservoirs and evaluate latency-reversing agents (LRAs). However, VOA can only reactivate a small fraction of intact proviruses. METHODS: To explore the utility of NOD scid gamma (NSG) mice as an in vivo model to reactivate HIV-1 proviruses from VOA-negative CD4+ T cells, resting CD4+ T cells from an HIV-1 latently infected individual were isolated and the human CD4+ T cells corresponding to VOA-positive and VOA-negative CD4+ T cells were engrafted into NSG mice...
January 1, 2017: Journal of Virus Eradication
https://www.readbyqxmd.com/read/28275453/insight-into-hiv-2-latency-may-disclose-strategies-for-a-cure-for-hiv-1-infection
#7
EDITORIAL
Suha Saleh, Lenard Vranckx, Rik Gijsbers, Frauke Christ, Zeger Debyser
HIV-1 and HIV-2 originate from two distinct zoonotic transmissions of simian immunodeficiency viruses from primate to human. Although both share similar modes of transmission and can result in the development of AIDS with similar clinical manifestations, HIV-2 infection is generally milder and less likely to progress to AIDS. HIV is currently incurable due to the presence of HIV provirus integrated into the host DNA of long-lived memory cells of the immune system without active replication. As such, the latent virus is immunologically inert and remains insensitive to the administered antiviral drugs targeting active viral replication steps...
January 1, 2017: Journal of Virus Eradication
https://www.readbyqxmd.com/read/28272134/romidepsin-induced-hiv-1-viremia-during-effective-antiretroviral-therapy-contains-identical-viral-sequences-with-few-deleterious-mutations
#8
Anni Winckelmann, Kirston Barton, Bonnie Hiener, Timothy E Schlub, Wei Shao, Thomas A Rasmussen, Lars Østergaard, Ole S Søgaard, Martin Tolstrup, Sarah Palmer
OBJECTIVE: To investigate the origin of the HIV-1 viremia induced by the latency-reversing agent romidepsin. DESIGN: Six individuals on suppressive antiretroviral therapy received romidepsin administered intravenously once weekly for 3 consecutive weeks. CD4 T cells were obtained at baseline, following the second and third romidepsin infusion, and 10 weeks after the final romidepsin treatment. Plasma samples were collected 24 and 72 h after romidepsin infusions...
March 27, 2017: AIDS
https://www.readbyqxmd.com/read/28258391/underlying-mechanisms-of-hiv-1-latency
#9
REVIEW
Bizhan Romani, Elham Allahbakhshi
Similarly to other retroviruses, HIV-1 integrates its genome into the cellular chromosome. Expression of viral genes from the integrated viral DNA could then be regulated by the host genome. If the infected cell suppresses viral gene expression, the virus will undergo latency. The latently infected cells cannot be detected or cleared by the immune system since they do not express viral antigens. These cells remain undetected for several years, even under antiretroviral treatments. The silenced HIV-1 DNA could be reactivated under certain conditions...
March 3, 2017: Virus Genes
https://www.readbyqxmd.com/read/28246360/multiple-histone-lysine-methyltransferases-are-required-for-the-establishment-and-maintenance-of-hiv-1-latency
#10
Kien Nguyen, Biswajit Das, Curtis Dobrowolski, Jonathan Karn
We showed previously that the histone lysine methyltransferase (HKMT) H3K27me3 (EZH2) is the catalytic subunit of Polycomb repressive complex 2 (PRC2) and is required for the maintenance of HIV-1 latency in Jurkat T cells. Here we show, by using chromatin immunoprecipitation experiments, that both PRC2 and euchromatic histone-lysine N-methyltransferase 2 (EHMT2), the G9a H3K9me2-3 methyltransferase, are highly enriched at the proviral 5' long terminal repeat (LTR) and rapidly displaced upon proviral reactivation...
February 28, 2017: MBio
https://www.readbyqxmd.com/read/28225830/ex-vivo-activation-of-cd4-t-cells-from-donors-on-suppressive-art-can-lead-to-sustained-production-of-infectious-hiv-1-from-a-subset-of-infected-cells
#11
John K Bui, Elias K Halvas, Elizabeth Fyne, Michele D Sobolewski, Dianna Koontz, Wei Shao, Brian Luke, Feiyu F Hong, Mary F Kearney, John W Mellors
The fate of HIV-infected cells after reversal of proviral latency is not well characterized. Simonetti, et al. recently showed that CD4+ T-cells containing intact proviruses can clonally expand in vivo and produce low-level infectious viremia. We hypothesized that reversal of HIV latency by activation of CD4+ T-cells can lead to the expansion of a subset of virus-producing cells rather than their elimination. We established an ex vivo cell culture system involving stimulation of CD4+ T-cells from donors on suppressive antiretroviral therapy (ART) with PMA/ionomycin (day 1-7), followed by rest (day 7-21), and then repeat stimulation (day 21-28), always in the presence of high concentrations of raltegravir and efavirenz to effectively block new cycles of viral replication...
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28202759/relationship-between-measures-of-hiv-reactivation-and-the-decline-of-latent-reservoir-under-latency-reversing-agents
#12
Janka Petravic, Thomas A Rasmussen, Sharon R Lewin, Stephen J Kent, Miles P Davenport
Antiretroviral-free HIV remission requires substantial reduction of the number of latently infected cells and enhanced immune control of viremia. Latency-reversing agents (LRA) aim to eliminate latently infected cells by increasing the rate of reactivation of HIV transcription, which exposes these cells to killing by the immune system. As LRA are explored in clinical trials, it becomes increasingly important to assess the effect of increased HIV reactivation rate on the decline of latently infected cells, and estimate LRA efficacy in increasing virus reactivation...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28196049/hiv-infection-in-the-native-and-allograft-kidney-implications-for-management-diagnosis-and-transplantation
#13
Véronique Avettand-Fenoël, Christine Rouzioux, Christophe Legendre, Guillaume Canaud
The native kidney is a reservoir for HIV-1 and a site of viral replication, similar to lymphoid tissue, gut-associated lymphoid tissue or semen. The ability of the virus to persist may result from either a true latency or sequestration in an anatomic site that is not effectively exposed to antiretroviral therapy. The presence of HIV in kidney epithelial cells will lead progressively to end-stage renal disease. For decades, HIV-infected patients were excluded from consideration for kidney transplantation. Hemodialysis and peritoneal dialysis were the only forms of treatment available to these patients...
February 11, 2017: Transplantation
https://www.readbyqxmd.com/read/28194140/hiv-1-tat-and-viral-latency-what-we-can-learn-from-naturally-occurring-sequence-variations
#14
REVIEW
Doreen Kamori, Takamasa Ueno
Despite the effective use of antiretroviral therapy, the remainder of a latently HIV-1-infected reservoir mainly in the resting memory CD4(+) T lymphocyte subset has provided a great setback toward viral eradication. While host transcriptional silencing machinery is thought to play a dominant role in HIV-1 latency, HIV-1 protein such as Tat, may affect both the establishment and the reversal of latency. Indeed, mutational studies have demonstrated that insufficient Tat transactivation activity can result in impaired transcription of viral genes and the establishment of latency in cell culture experiments...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28181540/hiv-related-proteins-prolong-macrophage-survival-through-induction-of-triggering-receptor-expressed-on-myeloid-cells-1
#15
Zhihong Yuan, Xian Fan, Bashar Staitieh, Chetna Bedi, Paul Spearman, David M Guidot, Ruxana T Sadikot
Triggering receptor expressed on myeloid cells-1(TREM-1) is a member of the superimmunoglobulin receptor family. We have previously shown that TREM-1 prolongs survival of macrophages treated with lipoolysaccharide through Egr2-Bcl2 signaling. Recent studies suggest a role for TREM-1 in viral immunity. Human immunodeficiency virus-1 (HIV) targets the monocyte/macrophage lineage at varying stages of infection. Emerging data suggest that macrophages are key reservoirs for latent HIV even in individuals on antiretroviral therapy...
February 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28166799/toll-like-receptor-3-activation-selectively-reverses-hiv-latency-in-microglial-cells
#16
David Alvarez-Carbonell, Yoelvis Garcia-Mesa, Stephanie Milne, Biswajit Das, Curtis Dobrowolski, Roxana Rojas, Jonathan Karn
BACKGROUND: Multiple toll-like receptors (TLRs) are expressed in cells of the monocytic lineage, including microglia, which constitute the major reservoir for human immunodeficiency virus (HIV) infection in the brain. We hypothesized that TLR receptor mediated responses to inflammatory conditions by microglial cells in the central nervous system (CNS) are able to induce latent HIV proviruses, and contribute to the etiology of HIV-associated neurocognitive disorders. RESULTS: Newly developed human microglial cell lines (hµglia), obtained by immortalizing human primary microglia with simian virus-40 (SV40) large T antigen and the human telomerase reverse transcriptase, were used to generate latently infected cells using a single-round HIV virus carrying a green fluorescence protein reporter (hµglia/HIV, clones HC01 and HC69)...
February 6, 2017: Retrovirology
https://www.readbyqxmd.com/read/28161963/effects-of-heme-degradation-products-on-reactivation-of-latent-hiv-1
#17
P Shankaran, M Madlenakova, V Hajkova, D Jilich, I Svobodova, A Horinek, Y Fujikura, Z Melkova
Human immunodeficiency virus (HIV-1) infection can be currently controlled by combined antiretroviral therapy, but a sterilizing cure is not achievable as this therapy does not target persistent HIV-1 in latent reservoirs. Therefore, different latency reversal agents are intensively explored in various models. We have previously observed that heme arginate, a drug approved for human use, reveals a strong synergism with PKC inducers in reactivation of the latent provirus. Heme is physiologically decomposed by heme oxygenases into 3 degradation products: iron (Fe2+), carbon monoxide (CO) and biliverdin which is further converted to bilirubin by biliverdin reductase...
February 6, 2017: Acta Virologica
https://www.readbyqxmd.com/read/28152383/htlv-1-tax-activates-hiv-1-transcription-in-latency-models
#18
Victor Emmanuel Viana Geddes, Diego Pandeló José, Fabio E Leal, Douglas F Nixon, Amilcar Tanuri, Renato Santana Aguiar
HIV-1 latency is a major obstacle to HIV-1 eradication. Coinfection with HTLV-1 has been associated with faster progression to AIDS. HTLV-1 encodes the transactivator Tax which can activate both HTLV-1 and HIV-1 transcription. Here, we demonstrate that Tax activates HIV transcription in latent CD4(+) T cells. Tax promotes the activation of P-TEFb, releasing CDK9 and Cyclin T1 from inactive forms, promoting transcription elongation and reactivation of latent HIV-1. Tax mutants lacking interaction with the HIV-1-LTR promoter were not able to activate P-TEFb, with no subsequent activation of latent HIV...
January 30, 2017: Virology
https://www.readbyqxmd.com/read/28147284/benzotriazoles-reactivate-latent-hiv-1-through-inactivation-of-stat5-sumoylation
#19
Alberto Bosque, Kyle A Nilson, Amanda B Macedo, Adam M Spivak, Nancie M Archin, Ryan M Van Wagoner, Laura J Martins, Camille L Novis, Matthew A Szaniawski, Chris M Ireland, David M Margolis, David H Price, Vicente Planelles
The presence of latent HIV-1 in infected individuals represents a major barrier preventing viral eradication. For that reason, reactivation of latent viruses in the presence of antiretroviral regimens has been proposed as a therapeutic strategy to achieve remission. We screened for small molecules and identified several benzotriazole derivatives with the ability to reactivate latent HIV-1. In the presence of IL-2, benzotriazoles reactivated and reduced the latent reservoir in primary cells, and, remarkably, viral reactivation was achieved without inducing cell proliferation, T cell activation, or cytokine release...
January 31, 2017: Cell Reports
https://www.readbyqxmd.com/read/28128418/p2x7-receptor-in-the-hippocampus-is-involved-in-gp120-induced-cognitive-dysfunction
#20
Y Liu, G Q Chen, B Y Liu, Q Chen, Y M Qian, S S Qin, C L Liu, C S Xu
To investigate the role of the P2X7 receptor in learning and memory dysfunction induced by HIV-1 envelope glycoprotein gp120 (gp120), we established HIV-1-associated dementia (HAD) animal models by intracerebroventricular (ICV) infusion of gp120 in rats. We observed gp120-induced cognitive dysfunction in the radial arm water maze test. Results showed that rats in the gp120 groups had longer escape latencies and more errors compared to those in the control group. For example, the average trial time in the 50-ng/day-gp120 group on day eight (16...
January 23, 2017: Genetics and Molecular Research: GMR
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