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https://www.readbyqxmd.com/read/28498985/hiv-antibodies-detect-hiv-persistence-and-low-level-viral-replication
#1
Sheila M Keating, Christopher D Pilcher, Vivek Jain, Mila Lebedeva, Dylan Hampton, Mohamed Abdel-Mohsen, Xutao Deng, Gary Murphy, Alex Welte, Shelley N Facente, Frederick Hecht, Steven G Deeks, Satish K Pillai, Michael P Busch
BACKGROUND: HIV antibodies are generated and maintained by ongoing systemic expression of HIV antigen. We investigated whether HIV antibody responses as measured by high-throughput quantitative and qualitative assays could be used to indirectly measure persistent HIV replication in individuals on antiretroviral therapy (ART). METHODS: HIV antibody measurements were made over time on and off suppressive ART and were compared to measures of HIV reservoir size and expression of anti-viral restriction factors...
May 11, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28497113/toward-a-cure-does-host-immunity-play-a-role
#2
Jielin Zhang, Clyde S Crumpacker
Three decades of research on human immunodeficiency virus (HIV) and AIDS reveal that the human body has developed through evolution a genome immune system embodying epigenetic regulation against pathogenic nucleic acid invasion. In HIV infection, this epigenetic regulation plays a cardinal role in HIV RNA production that silences HIV transcription at a molecular (RNA) level, controls viral load at a cellular (biological) level, and governs the viremic stage of AIDS at the clinical (patient) level. Even though the human genome is largely similar among humans and HIV is a single viral species, human hosts show significant differences in viral RNA levels, ranging from cell to organ to individual and expressed as elite controllers, posttreatment controllers, and patients with AIDS...
March 2017: MSphere
https://www.readbyqxmd.com/read/28468877/preservation-of-peripheral-t-follicular-helper-cell-function-in-hiv-controllers
#3
Supranee Buranapraditkun, Franco Pissani, Jeffrey E Teigler, Bruce T Schultz, Galit Alter, Mary Marovich, Merlin L Robb, Michael A Eller, Jeff Martin, Steven Deeks, Nelson L Michael, Hendrik Streeck
The maturation process of high-affinity antibodies is a result of intricate interactions between B cells and follicular helper T (Tfh) cells occurring in lymphoid germinal centers. HIV infection induces significant chronic immune activation, phenotypic skewing, and inflammation driven by years of continuous viral replication. High levels of viremia as well as immune activation and dysfunction have been demonstrated to have a perturbing impact on the B cell memory compartment and contribute to B cell exhaustion...
May 3, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28467486/the-effect-of-ingenol-b-on-the-suppressive-capacity-of-elite-suppressor-hiv-specific-cd8-t-cells
#4
Abena K Kwaa, Kennedy Goldsborough, Victoria E Walker-Sperling, Luiz F Pianowski, Lucio Gama, Joel N Blankson
BACKGROUND: Some latency-reversing agents (LRAs) inhibit HIV-specific CD8+ T cell responses. In a prior study of protein kinase C (PKC) agonists, we found that bryostatin-1 inhibited elite controller/suppressor (ES) CD8+ T cell suppressive activity whereas prostratin had no effect. Ingenol-B is another PKC agonist with potent LRA activity both by itself and in combination with the bromodomain inhibitor JQ1; however its effect on CD8+ T cell mediated control of HIV-1 replication is unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28464889/highly-divergent-patterns-of-genetic-diversity-and-evolution-in-proviral-quasispecies-from-hiv-controllers
#5
Suwellen S D de Azevedo, Diogo Gama Caetano, Fernanda H Côrtes, Sylvia L M Teixeira, Karina Dos Santos Silva, Brenda Hoagland, Beatriz Grinsztejn, Valdilea G Veloso, Mariza G Morgado, Gonzalo Bello
BACKGROUND: Ongoing intra-host HIV-1 evolution has been shown in individuals that naturally suppress the viremia to low levels (HIV controllers) by the analysis of the RNA in plasma compartment. Detection of evolution at the DNA proviral compartment in HIV controllers, however, has been more challenging and the precise correlation between the systemic viral suppression level and rate of reservoir's reseeding in those individuals is not fully understood. In this sense, we examined the proviral DNA quasispecies by single genome amplification of the env gene in a cohort of 23 HIV controllers from Brazil, divided in three groups, according to the level of systemic viral suppression: (1) elite controllers with persistent undetectable viral load (PEC, n = 6); (2) elite controllers with occasional episodes of transient (51-400 copies/mL) viremia (EEC, n = 7); and (3) viremic controllers with persistent low-level (80-2000 copies/mL) viremia (VC, n = 10)...
May 2, 2017: Retrovirology
https://www.readbyqxmd.com/read/28428094/cxcr6-gene-characterization-in-two-ethnically-distinct-south-african-populations-and-association-with-viraemic-disease-control-in-hiv-1-infected-black-south-african-individuals
#6
Anabela C P Picton, Maria Paximadis, Richard E Chaisson, Neil A Martinson, Caroline T Tiemessen
CXCR6 genetic variation was described for HIV-1-uninfected black (n=41) and Caucasian (n=40) South Africans. We also investigated the CXCR6 rs2234358 and rs2234355 single nucleotide polymorphisms in HIV-1 disease control in 124 HIV-1-infected drug-naïve black individuals [elite controllers (n=11), viraemic controllers (VCs, n=30), high viral load long-term nonprogressors (HVL LTNPs, n=11) and progressors (n=72)] compared to healthy controls (HCs; n=232). The rs2234358-T allele was underrepresented in VCs (40...
April 18, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28396665/negative-checkpoint-regulatory-molecule-2b4-cd244-upregulation-is-associated-with-invariant-natural-killer-t-cell-alterations-and-human-immunodeficiency-virus-disease-progression
#7
Fareed Ahmad, Esaki M Shankar, Yean K Yong, Hong Y Tan, Gerrit Ahrenstorf, Roland Jacobs, Marie Larsson, Reinhold E Schmidt, Adeeba Kamarulzaman, Abdul W Ansari
The CD1d-restricted invariant natural killer T (iNKT) cells are implicated in innate immune responses against human immunodeficiency virus (HIV). However, the determinants of cellular dysfunction across the iNKT cells subsets are seldom defined in HIV disease. Herein, we provide evidence for the involvement of the negative checkpoint regulator (NCR) 2B4 in iNKT cell alteration in a well-defined cohort of HIV-seropositive anti-retroviral therapy (ART) naïve, ART-treated, and elite controllers (ECs). We report on exaggerated 2B4 expression on iNKT cells of HIV-infected treatment-naïve individuals...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28386076/quantitative-humoral-profiling-of-the-hiv-1-proteome-in-elite-controllers-and-patients-with-very-long-term-efficient-antiretroviral-therapy
#8
Wang Zhang, Mohammed M Morshed, Kajsa Noyan, Aman Russom, Anders Sönnerborg, Ujjwal Neogi
A major challenge in evaluating the success of HIV eradication approaches is the need for accurate measurement of persistent HIV during effective antiretroviral therapy (ART). Previous studies have reported that the anti-HIV antibody assay "luciferase immuno-precipitation systems (LIPS)" can distinguish HIV-infected individuals harboring different sizes of the viral reservoirs. We performed antibody profiling of HIV-1 proteomes using LIPS in viremic progressors (n = 38), elite controllers (ECs; n = 19) and patients with fully suppressive long-term antiretroviral therapy (ART) (n = 19) (mean 17 years)...
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28350860/uniquely-altered-transcripts-are-associated-with-immune-preservation-in-hiv-infection
#9
Michelle Zanoni, Ítalo Karmann Aventurato, James Hunter, Maria Cecilia Araripe Sucupira, Ricardo Sobhie Diaz
The mechanisms underlying host HIV control hold much promise in the search for a functional HIV cure. We investigated the host genomic signatures in elite controllers or rapid progressors following recent infection and the correlates of immune reconstitution during combination antiretroviral therapy. We characterized the HIV-specific longitudinal host transcriptional response of peripheral blood mononuclear cells from elite controllers, rapid progressors, immune responders and non-responders using a RT-qPCR array in a cohort of recently HIV-infected Brazilian individuals...
2017: PloS One
https://www.readbyqxmd.com/read/28284876/dual-immunity-concomitantly-suppresses-hiv-1-progression
#10
Huma Qureshi, Jayanta Bhattacharya
Broadly neutralizing antibodies (bnAbs) elicited in HIV-1(+) elite neutralizers typically are unable to reduce viremia in the same individuals from whom they are isolated. A recent study reports the development of bnAbs in an elite controller that, along with the help of T cells, were associated with restricting HIV-1 progression.
May 2017: Trends in Microbiology
https://www.readbyqxmd.com/read/28225449/ifn-%C3%AE-augments-natural-killer-mediated-antibody-dependent-cellular-cytotoxicity-of-hiv-1-infected-autologous-cd4-t-cells-regardless-of-major-histocompatibility-complex-class-1-downregulation
#11
Costin Tomescu, Pablo Tebas, Luis J Montaner
DESIGN: We have previously shown that IFN-α stimulation augments direct natural killer (NK) cell lysis of autologous CD4 primary T cells infected with certain HIV-1 isolates based upon major histocompatibility complex class 1 (MHC-1) 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 prestimulation of NK cells could further enhance ADCC. METHODS: Using broadly neutralizing monoclonal antibodies against gp120 (VRC01 or PGV04) or plasma from HIV-1-infected patients (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...
March 13, 2017: AIDS
https://www.readbyqxmd.com/read/28211903/activating-killer-immunoglobulin-receptors-and-hla-c-a-successful-combination-providing-hiv-1-control
#12
Mauro S Malnati, Elisabetta Ugolotti, Maria Cristina Monti, Davide De Battista, Irene Vanni, Domenico Bordo, Francesca Sironi, Patrizia Larghero, Eddi Di Marco, Priscilla Biswas, Guido Poli, Elisa Vicenzi, Agostino Riva, Maciej Tarkowski, Giuseppe Tambussi, Silvia Nozza, Gino Tripodi, Francesco Marras, Andrea De Maria, Angela Pistorio, Roberto Biassoni
Several studies demonstrated a relevant role of polymorphisms located within the HLA-B and -C loci and the Killer Immunoglobulin Receptors (KIRs) 3DL1 and 3DS1 in controlling HIV-1 replication. KIRs are regulatory receptors expressed at the surface of NK and CD8+ T-cells that specifically bind HLA-A and -B alleles belonging to the Bw4 supratype and all the -C alleles expressing the C1 or C2 supratype. We here disclose a novel signature associated with the Elite Controller but not with the long-term nonprogressor status concerning 2DS activating KIRs and HLA-C2 alleles insensitive to miRNA148a regulation...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28193736/down-regulation-of-cd73-on-b-cells-of-patients-with-viremic-hiv-correlates-with-b-cell-activation-and-disease-progression
#13
Eun-Seong Kim, Christin Ackermann, Ilona Tóth, Patrick Dierks, Johanna M Eberhard, Raluca Wroblewski, Felix Scherg, Matthias Geyer, Reinhold E Schmidt, Claudia Beisel, Maximilian Bockhorn, Friedrich Haag, Jan van Lunzen, Julian Schulze Zur Wiesch
Recently, alterations of the T cell expression of the ectonucleotidases, CD39 and CD73, during HIV infection have been described. Here, peripheral (n = 70) and lymph nodal B cells (n = 10) of patients with HIV at different stages of disease as well as uninfected individuals were analyzed via multicolor flow cytometry with regard to expression of CD39 and CD73 and differentiation, proliferation, and exhaustion status. Patients with chronic, untreated HIV showed a significantly decreased frequency of CD73-expressing B cells (P < 0...
May 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28182614/similar-immunological-profiles-between-nonprogressing-hiv-infection-in-children-and-nonpathogenic-siv-infection
#14
Eva Poveda, Enrique Martin-Gayo
In the absence of antirretroviral therapy (ART), HIV infection leads to progression to AIDS in most infected individuals. However, there is a small group of HIV-infected patients capable of spontaneously controlling HIV infection, known as the elite controllers (less than 1% of total infected population). These patients maintain undetectable levels of HIV replication, in part, due to a continuously effective HIV specific T cell response. Moreover, in HIV-infected patients with suppressed viremia under ART, a chronic activation of the immune system persist, which can be related to a poor clinical outcome including death, development of co-morbidities, AIDS and non-AIDS defining events...
January 2017: AIDS Reviews
https://www.readbyqxmd.com/read/28077649/t-cell-receptor-tcr-clonotype-specific-differences-in-inhibitory-activity-of-hiv-1-cytotoxic-t-cell-clones-is-not-mediated-by-tcr-alone
#15
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 progressors. To define the role of individual T-cell receptor (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)...
March 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28069446/rich2-is-implicated-in-viraemic-control-of-hiv-1-in-black-south-african-individuals
#16
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)...
April 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
#17
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
#18
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 from those who require ART to suppress viral replication. We measured 87 cytokines in four groups of women: 73 ECs, 42 with pharmacologically suppressed viremia (ART), 42 with uncontrolled viral replication (noncontrollers [NCs]), and 48 HIV-uninfected (NEG) subjects...
March 15, 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
#19
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
#20
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
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