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"Elite control"

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
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...
November 21, 2016: AIDS Research and Human Retroviruses
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
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
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
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)
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
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
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
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
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
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
Lander Egaña-Gorroño, Alberto C Guardo, Manel E Bargalló, Evarist Planet, Elisenda Vilaplana, Tuixent Escribà, Iñaki Pérez, Josep Maria Gatell, Felipe García, Mireia Arnedo, Montserrat Plana M
BACKGROUND: The relationship between host microRNAs (miRNA), viral control and immune response has not yet been elucidated in the field of HIV. The aim of this study was to assess the differential miRNA profile in CD8+ T-cells between HIV-infected individuals who differ in terms of viral replication control and immune response. METHODS: miRNA profile from resting and CD3/CD28-stimulated CD8+ T-cells from uninfected individuals (HIV-, n = 11), Elite Controllers (EC, n = 15), Viremic Controllers (VC, n = 15), Viremic Progressors (VP, n = 13) and HIV-infected patients on therapy (ART, n = 14) was assessed using Affymetrix miRNA 3...
2016: PloS One
Wei Lu, Song Chen, Chunhui Lai, Mingyue Lai, Hua Fang, Hong Dao, Jun Kang, Jianhua Fan, Weizhong Guo, Linchun Fu, Jean-Marie Andrieu
We previously demonstrated in the Chinese macaque model that an oral vaccine made of inactivated SIV and Lactobacillus plantarum induced CD8(+) regulatory T-cells, which suppressed the activation of SIV(+)CD4(+) T-cells, prevented SIV replication, and protected macaques from SIV challenges. Here, we sought whether a similar population of CD8(+) T-regs would induce the suppression of HIV replication in elite controllers (ECs), a small population (3‰) of HIV-infected patients with undetectable HIV replication...
2016: Frontiers in Immunology
Yanina Ghiglione, María Julia Ruiz, Jimena Salido, César Trifone, Omar Sued, Yamila Martin, Patricia Patterson, Natalia Laufer, Gabriela Turk
OBJECTIVE: To evaluate the impact of chikungunya virus (CHIKV) infection on the quality of the HIV-specific CD8 T-cell (CTL) response in an HIV elite controller. DESIGN: Three blood samples were obtained from an elite controller at 27 days (EC-CHIKV, Sample 1, S1), 41 days (S2) and 1 year (S3) after CHIKV infection. Additionally, samples from another nine elite controllers and nine viremic chronics were obtained. METHODS: CD4 T-cell counts, viral load and immune activation were recorded...
July 31, 2016: AIDS
Clarisa M Buckner, Lela Kardava, Xiaozhen Zhang, Kathleen Gittens, J Shawn Justement, Colin Kovacs, Adrian B McDermott, Yuxing Li, Mohammad M Sajadi, Tae-Wook Chun, Anthony S Fauci, Susan Moir
Human immunodeficiency virus (HIV)-specific B-cell responses in infected individuals are maintained by active HIV replication. Suppression of viremia by antiretroviral therapy (ART) leads to quantitative and qualitative changes that remain unclear. Accordingly, B-cell responses were investigated in elite controllers (ECs), who maintain undetectable HIV levels without ART, and in individuals whose viremia was suppressed by ART. Despite a higher HIV burden in the ART group, compared with the EC group, frequencies of HIV-specific B cells were higher in the EC group, compared with those in the ART group...
August 1, 2016: Journal of Infectious Diseases
G Nunnari, P Fagone, F Condorelli, F Nicoletti, L Malaguarnera, M Di Rosa
OBJECTIVES: T-cell repertoire dysfunction characterizes human immunodeficiency virus type 1 (HIV-1) infection, but the pathogenic mechanisms remain unclear. Disease progression is probably due to a profound dysregulation of Th1, Th2, Th17 and Treg patterns. The aim of this study was to analyze the features of CD4+ T cells in HIV-positive patients with different viroimmunological profile. METHODS: we used a gene expression dataset of CD4+ T cells from healthy donors, HIV+ naive patients and Elite Controllers (EC), obtained from the NCBI Gene Expression Omnibus (GEO, http://www...
July 2016: Cytokine
D Paquin-Proulx, C Ching, I Vujkovic-Cvijin, D Fadrosh, L Loh, Y Huang, M Somsouk, S V Lynch, P W Hunt, D F Nixon, D SenGupta
Invariant natural killer T (iNKT) cells are innate-like T cells that respond to lipid antigens presented by CD1d. These immunoregulatory cells have the capacity for rapid cytokine release after antigen recognition and are essential for the activation of multiple arms of the immune response. HIV-1 infection is associated with iNKT cell depletion in the peripheral blood; however, their role in the gastrointestinal-associated lymphoid tissue (GALT) is less well studied. Our results show that iNKT cells are found at a higher frequency in GALT compared with blood, particularly in HIV-1 elite controllers...
April 6, 2016: Mucosal Immunology
Vikram Mehraj, Mohammad-Ali Jenabian, Rosalie Ponte, Bertrand Lebouché, Cecilia Costiniuk, Réjean Thomas, Jean-Guy Baril, Roger LeBlanc, Joseph Cox, Cécile Tremblay, Jean-Pierre Routy
OBJECTIVE: Following tissue barrier breaches, interleukin-33 (IL-33) is released as an 'alarmin' to induce inflammation. Soluble suppression of tumorigenicity 2 (sST2), as an IL-33 decoy receptor, contributes to limit inflammation. We assessed the relationship between the IL-33/ST2 axis and markers of gut mucosal damage in patients with early (EHI) and chronic HIV infection (CHI) and elite controllers. DESIGN: Analyses on patients with EHI and CHI were conducted to determine IL-33/sST2 changes over time...
June 19, 2016: AIDS
Anupama Ganesh, Donna Lemongello, Evelyn Lee, Julia Peterson, Bridget E McLaughlin, April L Ferre, Geraldine M Gillespie, Dietmar Fuchs, Steven G Deeks, Peter W Hunt, Richard W Price, Serena S Spudich, Barbara L Shacklett
The central nervous system (CNS) is an important target of HIV, and cerebrospinal fluid (CSF) can provide a window into host-virus interactions within the CNS. The goal of this study was to determine whether HIV-specific CD8(+) T cells are present in CSF of HIV controllers (HC), who maintain low to undetectable plasma viremia without antiretroviral therapy (ART). CSF and blood were sampled from 11 HC, defined based on plasma viral load (VL) consistently below 2,000 copies/ml without ART. These included nine elite controllers (EC, plasma VL <40 copies/ml) and two viremic controllers (VC, VL 40-2,000 copies/ml)...
August 2016: AIDS Research and Human Retroviruses
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