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https://www.readbyqxmd.com/read/27905985/tlr7-8-agonist-induces-a-post-entry-samhd1-independent-block-to-hiv-1-infection-of-monocytes
#1
Henning Hofmann, Bénédicte Vanwalscappel, Nicolin Bloch, Nathaniel R Landau
BACKGROUND: Monocytes, the primary myeloid cell-type in peripheral blood, are resistant to HIV-1 infection as a result of the lentiviral restriction factor SAMHD1. Toll-like receptors recognize microbial pathogen components, inducing the expression of antiviral host proteins and proinflammatory cytokines. TLR agonists that mimic microbial ligands have been found to have activity against HIV-1 in macrophages. The induction of restriction factors in monocytes by TLR agonist activation has not been well studied...
December 1, 2016: Retrovirology
https://www.readbyqxmd.com/read/27898737/transcriptomic-analysis-implicates-the-p53-signaling-pathway-in-the-establishment-of-hiv-1-latency-in-central-memory-cd4-t-cells-in-an-in-vitro-model
#2
Cory H White, Bastiaan Moesker, Nadejda Beliakova-Bethell, Laura J Martins, Celsa A Spina, David M Margolis, Douglas D Richman, Vicente Planelles, Alberto Bosque, Christopher H Woelk
The search for an HIV-1 cure has been greatly hindered by the presence of a viral reservoir that persists despite antiretroviral therapy (ART). Studies of HIV-1 latency in vivo are also complicated by the low proportion of latently infected cells in HIV-1 infected individuals. A number of models of HIV-1 latency have been developed to examine the signaling pathways and viral determinants of latency and reactivation. A primary cell model of HIV-1 latency, which incorporates the generation of primary central memory CD4 T cells (TCM), full-length virus infection (HIVNL4-3) and ART to suppress virus replication, was used to investigate the establishment of HIV latency using RNA-Seq...
November 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27898590/reactivation-of-simian-immunodeficiency-virus-reservoirs-in-the-brain-of-virally-suppressed-macaques
#3
Lucio Gama, Celina M Abreu, Erin N Shirk, Sarah L Price, Ming Li, Greg M Laird, Kelly A Metcalf Pate, Stephen W Wietgrefe, Shelby L O'Connor, Luiz Pianowski, Ashley T Haase, Carine Van Lint, Robert F Siliciano, Janice E Clements
OBJECTIVE: Resting CD4 T cells have been recognized as the major cell reservoir of latent HIV-1 during antiretroviral therapy (ART). Using an simian immunodeficiency virus (SIV)/macaque model for AIDS and HIV-related neurocognitive disorders we assessed the contribution of the brain to viral latency and reactivation. DESIGN: Pigtailed macaques were dual inoculated with SIVDeltaB670 and SIV17E-Fr and treated with an efficacious central nervous system-penetrant ART...
January 2, 2017: AIDS
https://www.readbyqxmd.com/read/27898045/dendritic-cell-based-immunotherapies-to-fight-hiv-how-far-from-a-success-story-a-systematic-review-and-meta-analysis
#4
REVIEW
Antonio Victor Campos Coelho, Ronald Rodrigues de Moura, Anselmo Jiro Kamada, Ronaldo Celerino da Silva, Rafael Lima Guimarães, Lucas André Cavalcanti Brandão, Luiz Cláudio Arraes de Alencar, Sergio Crovella
The scientific community still faces the challenge of developing strategies to cure HIV-1. One of these pursued strategies is the development of immunotherapeutic vaccines based on dendritic cells (DCs), pulsed with the virus, that aim to boost HIV-1 specific immune response. We aimed to review DCs-based therapeutic vaccines reports and critically assess evidence to gain insights for the improvement of these strategies. We performed a systematic review, followed by meta-analysis and meta-regression, of clinical trial reports...
November 26, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27892873/evidence-of-disseminated-infection-by-mycobacterium-avium-subspecies-hominissuis-in-a-pet-ferret-mustela-putorius-furo
#5
Javier Bezos, Beatriz Álvarez-Carrión, Antonio Rodríguez-Bertos, Álvaro Fernández-Manzano, Lucía de Juan, Cristina Huguet, Víctor Briones, Beatriz Romero
The infection caused by the zoonotic opportunistic pathogen Mycobacterium avium subsp. hominissuis (Mah) was reported for the first time in a pet ferret. Both owners were HIV-positive. Euthanasia of the pet was recommended due to medical reasons and as a preventive action. Disseminated and open tuberculosis lesions were observed in the gastrointestinal and respiratory systems of the ferret. Ecographic and radiographic surveys showed a severe generalized lymphadenopathy, strong thickening of the gastric wall and peritoneum layer...
September 17, 2016: Research in Veterinary Science
https://www.readbyqxmd.com/read/27889530/identification-of-proximal-biomarkers-of-pkc-agonism-and-evaluation-of-their-role-in-hiv-reactivation
#6
Sai Vikram Vemula, Jill W Maxwell, Alexey Nefedov, Bang-Lin Wan, Justin Steve, William Newhard, Rosa I Sanchez, David Tellers, Richard J Barnard, Wade Blair, Daria Hazuda, Andrea L Webber, Bonnie J Howell
DESIGN: The HIV latent CD4(+) T cell reservoir is broadly recognized as a barrier to HIV cure. Induction of HIV expression using protein kinase C (PKC) agonists is one approach under investigation for reactivation of latently infected CD4(+) T cells (Beans et al., 2013; Abreu et al., 2014; Jiang et al., 2014; Jiang and Dandekar, 2015). We proposed that an increased understanding of the molecular mechanisms of action of PKC agonists was necessary to inform on biological signaling and pharmacodynamic biomarkers...
November 23, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27888531/fate-of-microglia-during-hiv-1-infection-from-activation-to-senescence
#7
REVIEW
Natalie C Chen, Andrea T Partridge, Christian Sell, Claudio Torres, Julio Martín-García
Microglia support productive human immunodeficiency virus type 1 (HIV-1) infection and disturbed microglial function could contribute to the development of HIV-associated neurocognitive disorders (HAND). Better understanding of how HIV-1 infection and viral protein exposure modulate microglial function during the course of infection could lead to the identification of novel therapeutic targets for both the eradication of HIV-1 reservoir and treatment of neurocognitive deficits. This review first describes microglial origins and function in the normal central nervous system (CNS), and the changes that occur during aging...
November 26, 2016: Glia
https://www.readbyqxmd.com/read/27881659/glycosyl-phosphatidylinositol-gpi-anchored-anti-hiv-scfv-efficiently-protect-cd4-t-cells-from-hiv-1-infection-and-deletion-in-hu-pbl-mice
#8
Chaobaihui Ye, Weiming Wang, Liang Cheng, Guangming Li, Michael Wen, Qi Wang, Qing Zhang, Dan Li, Paul Zhou, Lishan Su
: Despite the success in viral inhibition and CD4 T cell recovery by highly active antiretroviral treatment (HAART), HIV-1 is still not curable due to the persistence of HIV-1 reservoir during treatment. One patient with acute myeloid leukemia who received allogeneic hematopoietic stem cell transplantation from homozygous CCR5 Δ32 donor has had no detectable viremia for 9 years after HAART cessation. This case has inspired a field of HIV-1 cure research focusing on engineering HIV-1 resistance of permissive cells...
November 23, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27873219/immortalization-of-primary-microglia-a-new-platform-to-study-hiv-regulation-in-the-central-nervous-system
#9
Yoelvis Garcia-Mesa, Taylor R Jay, Mary Ann Checkley, Benjamin Luttge, Curtis Dobrowolski, Saba Valadkhan, Gary E Landreth, Jonathan Karn, David Alvarez-Carbonell
The major reservoirs for HIV in the CNS are in the microglia, perivascular macrophages, and to a lesser extent, astrocytes. To study the molecular events controlling HIV expression in the microglia, we developed a reliable and robust method to immortalize microglial cells from primary glia from fresh CNS tissues and commercially available frozen glial cells. Primary human cells, including cells obtained from adult brain tissue, were transformed with lentiviral vectors expressing SV40 T antigen or a combination of SVR40 T antigen and hTERT...
November 21, 2016: Journal of Neurovirology
https://www.readbyqxmd.com/read/27872306/paired-quantitative-and-qualitative-assessment-of-the-replication-competent-hiv-1-reservoir-and-comparison-with-integrated-proviral-dna
#10
Julio C C Lorenzi, Yehuda Z Cohen, Lillian B Cohn, Edward F Kreider, John P Barton, Gerald H Learn, Thiago Oliveira, Christy L Lavine, Joshua A Horwitz, Allison Settler, Mila Jankovic, Michael S Seaman, Arup K Chakraborty, Beatrice H Hahn, Marina Caskey, Michel C Nussenzweig
HIV-1-infected individuals harbor a latent reservoir of infected CD4(+) T cells that is not eradicated by antiretroviral therapy (ART). This reservoir presents the greatest barrier to an HIV-1 cure and has remained difficult to characterize, in part, because the vast majority of integrated sequences are defective and incapable of reactivation. To characterize the replication-competent reservoir, we have combined two techniques, quantitative viral outgrowth and qualitative sequence analysis of clonal outgrowth viruses...
November 21, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27862555/genomic-epidemiology-of-cryptococcus-yeasts-identifies-adaptation-to-environmental-niches-underpinning-infection-across-an-african-hiv-aids-cohort
#11
Mathieu Vanhove, Mathew A Beale, Johanna Rhodes, Duncan Chanda, Shabir Lakhi, Geoffrey Kwenda, Sile Molloy, Natasha Karunaharan, Neil Stone, Thomas S Harrison, Tihana Bicanic, Matthew C Fisher
Emerging infections caused by fungi have become a widely recognized global phenomenon and are causing an increasing burden of disease. Genomic techniques are providing new insights into the structure of fungal populations, revealing hitherto undescribed fine-scale adaptations to environments and hosts that govern their emergence as infections. Cryptococcal meningitis is a neglected tropical disease that is responsible for a large proportion of AIDS-related deaths across Africa; however, the ecological determinants that underlie a patient's risk of infection remain largely unexplored...
October 19, 2016: Molecular Ecology
https://www.readbyqxmd.com/read/27862491/alarmins-and-central-nervous-system-inflammation-in-hiv-associated-neurological-disorders
#12
M-L Gougeon
In the era of highly active antiretroviral therapy (HAART), HIV-1-associated neurocognitive disorders (HAND) persist in infected individuals with adequate immunological and virological status. Risk factors for cognitive impairment include hepatitis C virus co-infection, host genetic factors predisposing to HAND, the early establishment of the virus in the CNS and its persistence under HAART; thus, the CNS is an important reservoir for HIV. Microglial cells are permissive to HIV-1, and NLRP3 inflammasome-associated genes were found expressed in brains of HIV-1-infected persons, contributing to brain disease...
November 16, 2016: Journal of Internal Medicine
https://www.readbyqxmd.com/read/27858912/a-randomized-controlled-clinical-trial-on-the-impact-of-ccr5-blockade-with-maraviroc-in-early-infection-on-t-cell-dynamics
#13
Maile Y Karris, Anya Umlauf, Florin Vaida, Douglas Richman, Susan Little, Davey Smith
BACKGROUND: Initiation of antiretroviral therapy (ART) in early HIV infection demonstrates clinical benefits including enhanced CD4 T-lymphocyte recovery and minimization of the latent HIV reservoir. Whether ART intensification with CCR5 blockade provides additional benefits is unknown. TRIAL DESIGN: This randomized controlled trial evaluated the impact of maraviroc (MVC) intensification in persons starting ART in acute and early HIV (AEH, within 3 months of estimated date of infection)...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27855263/disruption-or-excision-of-provirus-as-an-approach-to-hiv-cure
#14
Keith R Jerome
An effective approach to HIV cure will almost certainly require a combination of strategies, including some means of reducing the latent HIV reservoir. Because the integrated HIV provirus represents the major source of viral persistence and reactivation, one attractive approach is the direct targeting of provirus for disruption or excision using targeted endonucleases, such as CRISPR/Cas9, zinc finger nucleases, TAL effector nucleases, or meganucleases (homing endonucleases). This article highlights some of the challenges for successful endonuclease therapy for HIV, including optimization of enzyme activity and specificity, the possible emergence of viral resistance, and most importantly, efficient in vivo delivery of the enzymes to a sufficient portion of the latent reservoir...
December 2016: AIDS Patient Care and STDs
https://www.readbyqxmd.com/read/27855060/establishment-and-stability-of-the-latent-hiv-1-dna-reservoir
#15
Johanna Brodin, Fabio Zanini, Lina Thebo, Christa Lanz, Göran Bratt, Richard A Neher, Jan Albert
HIV-1 infection cannot be cured because the virus persists as integrated proviral DNA in long-lived cells despite years of suppressive antiretroviral therapy (ART). In a previous paper (Zanini, 2015) we documented HIV-1 evolution 10 untreated patients. Here we characterize establishment, turnover, and evolution of viral DNA reservoirs in the same patients after 3-18 years of suppressive ART. A median of 14\% (range 0-42\%) of the DNA sequences were defective due to G-to-A hypermutation. Remaining DNA sequences showed no evidence of evolution over years of suppressive ART...
November 15, 2016: ELife
https://www.readbyqxmd.com/read/27853288/enhancing-virion-tethering-by-bst2-sensitizes-productively-and-latently-hiv-infected-t-cells-to-adcc-mediated-by-broadly-neutralizing-antibodies
#16
Tram N Q Pham, Sabelo Lukhele, Frédéric Dallaire, Gabrielle Perron, Éric A Cohen
Binding of anti-HIV antibodies (Abs) to envelope (Env) glycoproteins on infected cells can mark them for elimination via antibody-dependent cell-mediated cytotoxicity (ADCC). BST2, a type I interferon (IFN)-stimulated restriction factor that anchors nascent Env-containing virions at the surface of infected cells has been shown to enhance ADCC functions. In a comprehensive analysis of ADCC potency by neutralizing anti-HIV Abs (NAbs), we show in this study that NAbs are capable of mediating ADCC against HIV-infected T cells with 3BNC117, PGT126 and PG9 being most efficient...
November 17, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27852851/identification-of-human-anti-hiv-gp160-monoclonal-antibodies-that-make-effective-immunotoxins
#17
Seth H Pincus, Kejing Song, Grace A Maresh, Dean H Hamer, Dimiter S Dimitrov, Weizao Chen, Mei-Yun Zhang, Victor F Ghetie, Po-Ying Chan-Hui, James E Robinson, Ellen S Vitetta
: The envelope (Env) glycoprotein of HIV is the only intact viral protein expressed on the surface of both virions and infected cells. Env is the target of neutralizing antibodies (Abs) and has been the subject of intense study in efforts to produce HIV vaccines. Therapeutic anti-Env Abs can also exert antiviral effects via Fc-mediated effector mechanisms or as cytotoxic immunoconjugates, such as immunotoxins (ITs). In the course of screening monoclonal antibodies (MAbs) for their ability to deliver cytotoxic agents to infected or Env-transfected cells, we noted disparities in their functional activities...
November 16, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27837106/cutting-edge-t-regulatory-cell-depletion-reactivates-latent-simian-immunodeficiency-virus-siv-in-controller-macaques-while-boosting-siv-specific-t-lymphocytes
#18
Tianyu He, Egidio Brocca-Cofano, Benjamin B Policicchio, Ranjit Sivanandham, Rajeev Gautam, Kevin D Raehtz, Cuiling Xu, Ivona Pandrea, Cristian Apetrei
T regulatory cells (Tregs) are critical in shaping the latent HIV/SIV reservoir, as they are preferentially infected, reverse CD4(+) T cell activation status, and suppress CTL responses. To reactivate latent virus and boost cell-mediated immune responses, we performed in vivo Treg depletion with Ontak (denileukin diftitox) in two SIVsab-infected controller macaques. Ontak induced significant (>75%) Treg depletion and major CD4(+) T cell activation, and only minimally depleted CD8(+) T cells. The overall ability of Tregs to control immune responses was significantly impaired despite their incomplete depletion, resulting in both reactivation of latent virus (virus rebound to 10(3) viral RNA copies/ml plasma in the absence of antiretroviral therapy) and a significant boost of SIV-specific CD8(+) T cell frequency, with rapid clearance of reactivated virus...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27824629/reply-to-immunometabolism-may-provide-insights-into-novel-mechanisms-of-hiv-reservoir-persistence
#19
Brigitte Autran, Manuela Pogliaghi, Christine Katlama
No abstract text is available yet for this article.
November 28, 2016: AIDS
https://www.readbyqxmd.com/read/27824628/immunometabolism-may-provide-new-insights-into-novel-mechanisms-of-hiv-reservoir-persistence
#20
Clovis S Palmer, Suzanne M Crowe
No abstract text is available yet for this article.
November 28, 2016: AIDS
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