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"Elite control"

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https://www.readbyqxmd.com/read/28077649/tcr-clonotype-specific-differences-in-inhibitory-activity-of-hiv-1-cytotoxic-t-cell-clones-is-not-mediated-by-tcr-alone
#1
Nina C Flerin, Huabiao Chen, Tynisha D Glover, Pedro A Lamothe, Jian Hua Zheng, Justin W Fang, Zaza M Ndhlovu, Evan W Newell, Mark M Davis, Bruce D Walker, Harris Goldstein
: Functional analysis of T cell responses in HIV-infected individuals has indicated that virus-specific CD8(+) T cells with superior antiviral efficacy are well represented in HIV-1 controllers but are rare or absent in HIV-1 progessors. To define the role of individual TCR clonotypes in differential antiviral CD8(+) T cell function, we performed detailed functional and mass cytometric cluster analysis of multiple CD8(+) T cell clones recognizing the identical HLA-B*2705-restricted HIV-1 epitope KK10 (KRWIILGLNK)...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28069446/rich2-is-implicated-in-viraemic-control-of-hiv-1-in-black-south-african-individuals
#2
Maria Paximadis, Refilwe N Ngqobe, Richard E Chaisson, Neil A Martinson, Caroline T Tiemessen
An intronic single nucleotide polymorphism (SNP) in RICH2 (rs2072255; 255(i)), in complete linkage disequilibrium (LD) with an exonic SNP (rs2072254; 254(e)), has been identified in a genome wide association study to be associated with progression to AIDS in Caucasian individuals. RICH2 links tetherin to the cortical actin network and the RICH2/tetherin interaction has been shown to be important for the downstream activation of NF-κβ and the consequential promotion of proinflammatory responses. We investigated the role of these two SNPs in natural control of HIV-1 in black South Africans including healthy controls (HCs; N=102) and antiretroviral-naive HIV-1-infected controllers (HICs; N=52) and progressors (N=74)...
January 6, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28060015/ifn-%C3%AE-augments-nk-mediated-antibody-dependent-cellular-cytotoxicity-adcc-of-hiv-1-infected-autologous-cd4-t-cells-regardless-of-mhc-i-downregulation
#3
Costin Tomescu, Pablo Tebas, Luis J Montaner
DESIGN: We have previously shown that IFN-α stimulation augments direct NK cell lysis of autologous CD4 primary T cells infected with certain HIV-1 isolates based upon MHC-I downregulation capacity. Here, we investigated if Antibody Dependent Cellular Cytotoxicity (ADCC) could trigger lysis of HIV-1 isolates that were resistant to direct NK lysis and if IFN-α pre-stimulation of NK cells could further enhance ADCC. METHODS: Using broadly neutralizing monoclonal antibodies against gp120 (VRC01 or PGV04) or plasma from HIV-1 infected subjects (ART-suppressed or Elite Controller) to trigger ADCC, we measured NK cell chromium release cytotoxicity against HIV-1 infected autologous CD4 primary T cells and NK cell CD107a degranulation against gp120-coated CD4 T cells...
January 4, 2017: AIDS
https://www.readbyqxmd.com/read/28053103/cytokines-elevated-in-hiv-elite-controllers-reduce-hiv-replication-in-vitro-and-modulate-hiv-restriction-factor-expression
#4
Evan S Jacobs, Sheila M Keating, Mohamed Abdel-Mohsen, Stuart L Gibb, John W Heitman, Heather C Inglis, Jeffrey N Martin, Jinbing Zhang, Zhanna Kaidarova, Xutao Deng, Shiquan Wu, Kathryn Anastos, Howard Crystal, Maria C Villacres, Mary Young, Ruth M Greenblatt, Alan L Landay, Stephen J Gange, Steven G Deeks, Elizabeth T Golub, Satish K Pillai, Philip J Norris
: A subset of HIV infected individuals termed elite controllers (ECs) maintain CD4+ T cell counts and control viral replication in the absence of antiretroviral therapy (ART). Systemic cytokine responses may differentiate ECs from subjects with uncontrolled viral replication or those who require ART to suppress viral replication. We measured 87 cytokines in four groups of women: 73 EC, 42 with pharmacologically suppressed viremia (ART), 42 with uncontrolled viral replication (noncontrollers, NC), and 48 HIV uninfected (NEG) subjects...
January 4, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28039100/utility-of-systematic-isolation-of-immune-cell-subsets-from-hiv-infected-individuals-for-mirna-profiling
#5
Manel E Bargalló, Alberto C Guardo, Maria J Maleno, Laia Miralles, Lander Egaña-Gorroño, Tuixent Escribà, Felipe García, Jose M Gatell, Mireia Arnedo, Montserrat Plana
INTRODUCTION: Peripheral blood mononuclear cells (PBMCs) are frequently used for genomic analyses, but several factors can affect the yield and integrity of nucleic acids, including the methods of cell collection and isolation. The goal of this work was to analyze the utility of systematic isolation of different immune cell subsets by immunomagnetic separation and the RNA integrity after isolated cells from samples of HIV-infected patients. METHODS: PBMC from Healthy Controls (HC, n=15), Elite Controllers (EC, n=15), Viremic Controllers (VC, n=15), Viremic Progressors (VP, n=15) and HIV-infected patients on therapy (ART, n=15) were isolated by Ficoll-Paque density gradient centrifugation...
December 27, 2016: Journal of Immunological Methods
https://www.readbyqxmd.com/read/27941971/plasma-metabolomics-biosignature-according-to-hiv-stage-of-infection-pace-of-disease-progression-viremia-level-and-immunological-response-to-treatment
#6
Bruno Scarpelini, Michelle Zanoni, Maria Cecilia Araripe Sucupira, Hong-Ha M Truong, Luiz Mario Ramos Janini, Ismael Dale Cotrin Segurado, Ricardo Sobhie Diaz
BACKGROUND: We evaluated plasma samples HIV-infected individuals with different phenotypic profile among five HIV-infected elite controllers and five rapid progressors after recent HIV infection and one year later and from 10 individuals subjected to antiretroviral therapy, five of whom were immunological non-responders (INR), before and after one year of antiretroviral treatment compared to 175 samples from HIV-negative patients. A targeted quantitative tandem mass spectrometry metabolomics approach was used in order to determine plasma metabolomics biosignature that may relate to HIV infection, pace of HIV disease progression, and immunological response to treatment...
2016: PloS One
https://www.readbyqxmd.com/read/27926931/microbial-translocation-and-inflammation-occur-in-hyperacute-immunodeficiency-virus-infection-and-compromise-host-control-of-virus-replication
#7
Adam J Ericsen, Michael Lauck, Mariel S Mohns, Sarah R DiNapoli, James P Mutschler, Justin M Greene, Jason T Weinfurter, Gabrielle Lehrer-Brey, Trent M Prall, Samantha M Gieger, Connor R Buechler, Kristin A Crosno, Eric J Peterson, Matthew R Reynolds, Roger W Wiseman, Benjamin J Burwitz, Jacob D Estes, Jonah B Sacha, Thomas C Friedrich, Jason M Brenchley, David H O'Connor
Within the first three weeks of human immunodeficiency virus (HIV) infection, virus replication peaks in peripheral blood. Despite the critical, causal role of virus replication in determining transmissibility and kinetics of progression to acquired immune deficiency syndrome (AIDS), there is limited understanding of the conditions required to transform the small localized transmitted founder virus population into a large and heterogeneous systemic infection. Here we show that during the hyperacute "pre-peak" phase of simian immunodeficiency virus (SIV) infection in macaques, high levels of microbial DNA transiently translocate into peripheral blood...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926762/association-of-arterial-and-lymph-node-inflammation-with-distinct-inflammatory-pathways-in-human-immunodeficiency-virus-infection
#8
Ahmed Tawakol, Amorina Ishai, Danny Li, Richard A P Takx, Sophia Hur, Yannick Kaiser, Miguel Pampaloni, Adam Rupert, Denise Hsu, Irini Sereti, Rémi Fromentin, Nicolas Chomont, Peter Ganz, Steven G Deeks, Priscilla Y Hsue
Importance: Human immunodeficiency virus (HIV) infection is associated with a high risk of cardiovascular disease and increased arterial inflammation. In HIV, inflammation is also increased within lymph nodes (LNs), tissues known to harbor the virus even among treated and suppressed individuals. Objective: To test the hypothesis that arterial inflammation is linked to HIV disease activity and to inflammation within HIV-infected tissues (LNs). Design, Setting, and Participants: For this case-control study, participants were recruited from the SCOPE (Observational Study of the Consequences of the Protease Inhibitor Era) cohort, a clinic-based cohort of individuals receiving care at San Francisco General Hospital and the San Francisco Veteran's Affairs Medical Center...
December 7, 2016: JAMA Cardiology
https://www.readbyqxmd.com/read/27843442/changes-in-follicular-cd4-t-helper-cells-as-a-marker-for-evaluating-disease-progression-in-the-competition-between-hiv-and-host-immunity
#9
REVIEW
Xiaolei Wang, Widade Ziani, Huanbin Xu
Follicular CD4+ T helper (TFH) cells interact with B cells in follicular germinal centers and play a prominent role in promoting effective humoral immune responses to pathogens, providing help for B cell development and antibody affinity maturation. Recent studies indicate TFH cells are expanded in HIV/SIV chronic infection, or depleted in terminal stages of disease, yet relatively maintained in elite controllers when compared with uninfected controls. A better understanding of the mechanisms behind these immunologic abnormalities may lead to more effective vaccination and therapeutic strategies...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27771962/humoral-antibody-responses-to-hiv-viral-proteins-and-to-cd4-among-hiv-controllers-rapid-and-typical-progressors-in-an-hiv-positive-patient-cohort
#10
Elizabeth Fink, Katherine Fuller, Brian Agan, Edward A Berger, Andrew Saphire, Gerald V Quinnan, John H Elder
The purpose of this study was to assess humoral antibody responses as a function of disease progression (DP) in a well-defined HIV(+) cohort. We quantified antibodies to HIV-1 gp120, Gag, and CD4 receptor by enzyme-linked immunosorbent assay in sera from a cohort of 97 HIV(+) subjects at defined stages of DP. We also measured antibody-dependent cellular cytotoxicity (ADCC) as a function of the clinical status of the patients. We purified antibodies to CD4 and gp120 and assessed them for specificity, ability to block gp120 binding to target cells, ability to block virus infection, and ability to facilitate ADCC...
December 2016: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/27630237/monitoring-integration-over-time-supports-a-role-for-cytotoxic-t-lymphocytes-and-ongoing-replication-as-determinants-of-reservoir-size
#11
Marilia Rita Pinzone, Erin Graf, Lindsay Lynch, Brigit McLaughlin, Frederick M Hecht, Mark Connors, Stephen A Migueles, Wei-Ting Hwang, Giuseppe Nunnari, Una O'Doherty
: The dynamics of HIV reservoir accumulation off antiretroviral therapy (ART) is underexplored. Levels of integrated HIV DNA in peripheral blood mononuclear cells (PBMCs) were longitudinally monitored before and after antiviral therapy. HIV integration increased over time in both elite controllers (ECs; n = 8) and noncontrollers (NCs; n = 6) before ART, whereas integration remained stable in patients on ART (n = 4). The median annual fold change was higher in NCs than in ECs and negatively correlated with CD4/CD8 T-cell ratio...
December 1, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27600080/retrospective-proteomic-analysis-of-cellular-immune-responses-and-protective-correlates-of-p24-vaccination-in-an-hiv-elite-controller-using-antibody-arrays
#12
Suneth S Perera, Bin Wang, Arturo Damian, Wayne Dyer, Li Zhou, Viviane Conceicao, Nitin K Saksena
HIV p24 is an extracellular HIV antigen involved in viral replication. Falling p24 antibody responses are associated with clinical disease progression and their preservation with non-progressive disease. Stimulation of p24 antibody production by immunization to delay progression was the basis of discontinued p24 vaccine. We studied a therapy-naive HIV+ man from Sydney, Australia, infected in 1988. He received the HIV-p24-virus like particle (VLP) vaccine in 1993, and continues to show vigorous p24 antigen responses (>4% p24-specific CD4⁺ T cells), coupled with undetectable plasma viremia...
2016: Microarrays
https://www.readbyqxmd.com/read/27561453/blood-b-lymphocyte-stimulator-blys-baff-levels-may-reflect-natural-immunity-to-hiv-in-highly-exposed-uninfected-beninese-commercial-sex-workers
#13
Catherine Sabourin-Poirier, Lyvia Fourcade, Josiane Chagnon-Choquet, Annie-Claude Labbé, Michel Alary, Fernand Guédou, Johanne Poudrier, Michel Roger
We have previously shown that excess B lymphocyte Stimulator (BLyS)/BAFF in plasma and on surface of blood dendritic cells (DC) of HIV-infected progressors coincides with B-cell dysregulations and increased frequencies of "precursor" innate marginal zone (MZ)-like B-cells. In contrast, both blood BLyS levels and frequencies of this population remained unaltered in HIV elite-controllers. Based on these observations, we hypothesized that control of BLyS and innate B-cell status could be associated with natural immunity against HIV infection...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27537569/hepatic-fibrosis-and-immune-phenotype-vary-by-hcv-viremia-in-hcv-hiv-co-infected-subjects-a-women-s-interagency-hiv-study
#14
Seema N Desai, Jennifer L Dodge, Alan L Landay, Marshall J Glesby, Patricia S Latham, Maria C Villacres, Audrey L French, Stephen J Gange, Ruth M Greenblatt, Marion G Peters
HCV and HIV independently lead to immune dysregulation. The mechanisms leading to advanced liver disease progression in HCV/HIV coinfected subjects remain unclear.In this cross-sectional study, we assessed the association of HCV viremia, liver fibrosis, and immune response patterns in well-characterized HIV phenotypes: Elite controllers (Elites), HIV controlled (ARTc), and HIV uncontrolled (ARTuc) matched by age and race. Groups were stratified by HCV RNA status. Regulatory T-cell frequencies, T-cell activation (HLADR+CD38+), apoptosis (Caspase-3+), and intracellular cytokines (interferon-γ, IL-2, IL-17) were assessed using multiparametric flow-cytometry...
August 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27454561/viral-load-criteria-and-threshold-optimization-to-improve-hiv-incidence-assay-characteristics
#15
Reshma Kassanjee, Christopher D Pilcher, Michael P Busch, Gary Murphy, Shelley N Facente, Sheila M Keating, Elaine Mckinney, Kara Marson, Matthew A Price, Jeffrey N Martin, Susan J Little, Frederick M Hecht, Esper G Kallas, Alex Welte
OBJECTIVE: Assays for classifying HIV infections as 'recent' or 'nonrecent' for incidence surveillance fail to simultaneously achieve large mean durations of 'recent' infection (MDRIs) and low 'false-recent' rates (FRRs), particularly in virally suppressed persons. The potential for optimizing recent infection testing algorithms (RITAs), by introducing viral load criteria and tuning thresholds used to dichotomize quantitative measures, is explored. DESIGN: The Consortium for the Evaluation and Performance of HIV Incidence Assays characterized over 2000 possible RITAs constructed from seven assays (Limiting Antigen, BED, Less-sensitive Vitros, Vitros Avidity, BioRad Avidity, Architect Avidity, and Geenius) applied to 2500 diverse specimens...
September 24, 2016: AIDS
https://www.readbyqxmd.com/read/27445426/elite-capture-and-corruption-in-two-villages-in-bengkulu-province-sumatra
#16
Anton Lucas
This paper examines leadership, elite capture and corruption in two villages in Sumatra. It compares implementation and outcomes of several conservation and development projects in the context of democratization and decentralization reforms introduced in Indonesia since 1998. In examining aspects of elite control and elite capture, this paper focuses on the activities of local elites, particularly village officials, who use their positions to monopolize planning and management of projects that were explicitly intended to incorporate participatory and accountability features...
2016: Human Ecology: An Interdisciplinary Journal
https://www.readbyqxmd.com/read/27406996/elite-controller-cd8-t-cells-exhibit-comparable-viral-inhibition-capacity-but-better-sustained-effector-properties-compared-to-chronic-progressors
#17
David Shasha, Dan Karel, Olivia Angiuli, Adam Greenblatt, Musie Ghebremichael, Xu Yu, Filippos Porichis, Bruce D Walker
Mechanisms modulating HIV-specific CD8+ T cell-mediated viral inhibition are not well defined. To delineate features of effective control, we compared the ability of CD8(+) T cells from HIV ECs and CPs to inhibit HIV ex vivo. ECs showed superior inhibition compared to HAART-treated or untreated CPs in a typical VIA in which CD8+ T cells are rested 3 d before use (P = 0.025). In contrast, comparable antiviral activity was observed in freshly thawed cells. Rested CD8(+) T cells underwent apoptosis with preferential loss of HIV-specific cells...
December 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27403738/sequential-ccr5-tropic-hiv-1-reactivation-from-distinct-cellular-reservoirs-following-perturbation-of-elite-control
#18
Sarah A Watters, Petra Mlcochova, Frank Maldarelli, Nilu Goonetilleke, Deenan Pillay, Ravindra K Gupta
BACKGROUND: HIV Elite Controllers may reveal insights into virus persistence given they harbour small reservoir sizes, akin to HIV non-controllers treated early with combination antiretroviral therapy. Both groups of patients represent the most promising candidates for interventions aimed at sustained remission or 'cure'. Analytic treatment interruption (ATI) in the latter group leads to stochastic rebound of virus, though it is unclear whether loss of elite control is also associated with similar rebound characteristics...
2016: PloS One
https://www.readbyqxmd.com/read/27203285/fluctuations-in-blood-marginal-zone-b-cell-frequencies-may-reflect-migratory-patterns-associated-with-hiv-1-disease-progression-status
#19
Julie Gauvin, Josiane Chagnon-Choquet, Johanne Poudrier, Michel Roger
We have previously shown that overexpression of BLyS/BAFF was associated with increased relative frequencies of innate "precursor" marginal zone (MZ)-like B-cells in the blood of HIV-1-infected rapid and classic progressors. However, along with relatively normal BLyS/BAFF expression levels, these cells remain unaltered in elite-controllers (EC), rather, percentages of more mature MZ-like B-cells are decreased in the blood of these individuals. Fluctuations in frequencies of blood MZ-like B-cell populations may reflect migratory patterns associated with disease progression status, suggesting an important role for these cells in HIV-1 pathogenesis...
2016: PloS One
https://www.readbyqxmd.com/read/27177315/cancers-in-elite-controllers-appropriate-follow-up-is-essential
#20
Jason F Okulicz, Faroudy Boufassa, Dominique Costagliola, Anuradha Ganesan, Olivier Lambotte
Elite controllers may have non-AIDS-defining comorbidities. We describe here 18 cases of cancers diagnosed in two cohorts of controllers, elite and viremic. Cancers are similar to those commonly described in antiretroviral therapy treated patients but also in HIV-negative patients, which underlines the necessity of an appropriate regular follow-up.
July 17, 2016: AIDS
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