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"Elite control"

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https://www.readbyqxmd.com/read/28615199/impaired-downregulation-of-nkg2d-ligands-by-nef-protein-from-elite-controllers-sensitizes-hiv-1-infected-cells-to-adcc
#1
Nirmin Alsahafi, Jonathan Richard, Jérémie Prévost, Mathieu Coutu, Nathalie Brassard, Matthew S Parsons, Daniel E Kaufmann, Mark Brockman, Andrés Finzi
HIV-1 Nef clones isolated from a rare subset of HIV-1-infected elite controllers (EC), with the ability to suppress viral load to undetectable levels in the absence of antiretroviral therapy, are unable to fully downregulate CD4 from the plasma membrane of CD4+ T cells. Residual CD4 left at the plasma membrane allows Env-CD4 interaction, which leads to increased exposure of Env CD4-induced epitopes and increases susceptibility of infected cells to antibody-dependent cellular cytotoxicity (ADCC). ADCC is mediated largely by natural killer (NK) cells, which control their activation status through the cumulative signals received through activating and inhibitory receptors...
June 14, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28615147/hiv-specific-b-cell-frequency-correlates-with-neutralization-breadth-in-patients-naturally-controlling-hiv-infection
#2
Angeline Rouers, Jéromine Klingler, Bin Su, Assia Samri, Géraldine Laumond, Sophie Even, Véronique Avettand-Fenoel, Clemence Richetta, Nicodème Paul, Faroudy Boufassa, Laurent Hocqueloux, Hugo Mouquet, Christine Rouzioux, Olivier Lambotte, Brigitte Autran, Stéphanie Graff-Dubois, Christiane Moog, Arnaud Moris
HIV-specific broadly neutralizing antibodies (bnAbs) have been isolated from patients with high viremia but also from HIV controllers that repress HIV-1 replication. In these elite controllers (ECs), multiple parameters contribute to viral suppression, including genetic factors and immune responses. Defining the immune correlates associated with the generation of bnAbs may help in designing efficient immunotherapies. In this study, in ECs either positive or negative for the HLA-B*57 protective allele, in treated HIV-infected and HIV-negative individuals, we characterized memory B cell compartments and HIV-specific memory B cells responses using flow cytometry and ELISPOT...
May 31, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28604502/the-association-of-hiv-1-gag-specific-igg-antibodies-with-natural-control-of-hiv-1-infection-in-individuals-not-carrying-hla-b-57-01-is-only-observed-in-viremic-controllers
#3
M Christian Tjiam, Mazmah A Morshidi, Lucy Sariputra, Jeffrey N Martin, Steven G Deeks, Dino Tan, Silvia Lee, Sonia Fernandez, Martyn A French
To expand upon our previous observation that HIV-1 Gag-specific IgG antibodies were highest in HIV controllers not carrying HLA-B*57:01, we analysed these antibodies in a larger cohort of viremic controllers (VCs) or elite controllers (ECs) considering carriage of 'protective' HLA-B alleles. HIV-1 p24-specific IgG1 and IgG2 antibodies were higher only in HLA-B*57:01 VCs but there were no differences in ECs. Associations of HIV-1 gp140-specific IgG antibodies with HLA-B*57:01 carriage were inconsistent amongst VCs and ECs...
June 9, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28498985/hiv-antibodies-detect-hiv-persistence-and-low-level-viral-replication
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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...
July 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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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