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https://www.readbyqxmd.com/read/29134258/novel-full-length-major-histocompatibility-complex-class-i-allele-discovery-and-haplotype-definition-in-pig-tailed-macaques
#1
Matthew R Semler, Roger W Wiseman, Julie A Karl, Michael E Graham, Samantha M Gieger, David H O'Connor
Pig-tailed macaques (Macaca nemestrina, Mane) are important models for human immunodeficiency virus (HIV) studies. Their infectability with minimally modified HIV makes them a uniquely valuable animal model to mimic human infection with HIV and progression to acquired immunodeficiency syndrome (AIDS). However, variation in the pig-tailed macaque major histocompatibility complex (MHC) and the impact of individual transcripts on the pathogenesis of HIV and other infectious diseases is understudied compared to that of rhesus and cynomolgus macaques...
November 13, 2017: Immunogenetics
https://www.readbyqxmd.com/read/29134249/early-siv-and-hiv-infection-promotes-the-lilrb2-mhc-i-inhibitory-axis-in-cdcs
#2
Lamine Alaoui, Gustavo Palomino, Sandy Zurawski, Gerard Zurawski, Sixtine Coindre, Nathalie Dereuddre-Bosquet, Camille Lecuroux, Cecile Goujard, Bruno Vaslin, Christine Bourgeois, Pierre Roques, Roger Le Grand, Olivier Lambotte, Benoit Favier
Classical dendritic cells (cDCs) play a pivotal role in the early events that tip the immune response toward persistence or viral control. In vitro studies indicate that HIV infection induces the dysregulation of cDCs through binding of the LILRB2 inhibitory receptor to its MHC-I ligands and the strength of this interaction was proposed to drive disease progression. However, the dynamics of the LILRB2/MHC-I inhibitory axis in cDCs during early immune responses against HIV are yet unknown. Here, we show that early HIV-1 infection induces a strong and simultaneous increase of LILRB2 and MHC-I expression on the surface of blood cDCs...
November 13, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29127275/allogeneic-stem-cell-transplantation-in-fully-mhc-matched-mauritian-cynomolgus-macaques-recapitulates-diverse-human-clinical-outcomes
#3
Benjamin J Burwitz, Helen L Wu, Shaheed Abdulhaqq, Christine Shriver-Munsch, Tonya Swanson, Alfred W Legasse, Katherine B Hammond, Stephanie L Junell, Jason S Reed, Benjamin N Bimber, Justin M Greene, Gabriela M Webb, Mina Northrup, Wolfram Laub, Paul Kievit, Rhonda MacAllister, Michael K Axthelm, Rebecca Ducore, Anne Lewis, Lois M A Colgin, Theodore Hobbs, Lauren D Martin, Betsy Ferguson, Charles R Thomas, Angela Panoskaltsis-Mortari, Gabrielle Meyers, Jeffrey J Stanton, Richard T Maziarz, Jonah B Sacha
Allogeneic hematopoietic stem cell transplantation (HSCT) is a critically important therapy for hematological malignancies, inborn errors of metabolism, and immunodeficiency disorders, yet complications such as graft-vs.-host disease (GvHD) limit survival. Development of anti-GvHD therapies that do not adversely affect susceptibility to infection or graft-vs.-tumor immunity are hampered by the lack of a physiologically relevant, preclinical model of allogeneic HSCT. Here we show a spectrum of diverse clinical HSCT outcomes including primary and secondary graft failure, lethal GvHD, and stable, disease-free full donor engraftment using reduced intensity conditioning and mobilized peripheral blood HSCT in unrelated, fully MHC-matched Mauritian-origin cynomolgus macaques...
November 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/29118125/alt-803-transiently-reduces-siv-replication-in-the-absence-of-antiretroviral-treatment
#4
Amy L Ellis-Connell, Alexis J Balgeman, Katie R Zarbock, Gabrielle Barry, Andrea Weiler, Jack O Egan, Emily K Jeng, Thomas Friedrich, Jeffrey S Miller, Ashley T Haase, Timothy W Schacker, Hing C Wong, Eva Rakasz, Shelby L O'Connor
Developing biological interventions to control HIV replication in the absence of antiretroviral therapy (ART) could contribute to the development of a functional cure. As a potential alternative to ART, the IL-15 superagonist ALT-803 has been shown to boost the number and function of HIV-specific CD8(+) T and NK cell populations, in vitro. Four SIV(+) rhesus macaques, three of whom possessed MHC alleles associated with control of SIV, and all of whom had received SIV vaccine vectors that had the potential to elicit CD8(+) T cell responses, were given ALT-803 in three treatment cycles...
November 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29100330/protective-cellular-immunity-generated-by-cross-presenting-recombinant-overlapping-peptide-proteins
#5
Lili Cai, Jianbo Zhang, Renying Zhu, Weixing Shi, Xiaobing Xia, Mark Edwards, William Finch, Anthony Coombs, Ju Gao, Kangwen Chen, Sophie Owen, Shisong Jiang, Wenshu Lu
Priming of naive CD8(+) and CD4(+) T cells by dendritic cells (DCs) requires effective antigen presentation on both MHC class I and II molecules. We have developed a novel technology to use recombinant overlapping peptides (ROP) that stimulate both CD8(+) and CD4(+) T cell immune responses. The single chain protein of a ROP is made up of overlapping peptides linked by the target sequence (LRMK) for cathepsin S, a protease found in the endosomes of DCs. We designed synthetic genes encoding ROPs derived from ovalbumin (OVA), tuberculosis protein (CFP10-ESAT6), human papilloma virus (HPV) protein (E7) and survivin, a protein commonly over-expressed in tumour cells...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29055777/characterization-of-classical-major-histocompatibility-complex-mhc-class-ii-genes-in-northern-pig-tailed-macaques-macaca-leonina
#6
Xiao-Dong Lian, Xi-He Zhang, Zheng-Xi Dai, Yong-Tang Zheng
The northern pig-tailed macaque (Macaca leonina) has been identified as an independent species from the pig-tailed macaque group. The species is a promising animal model for HIV/AIDS pathogenesis and vaccine studies due to susceptibility to HIV-1. However, the major histocompatibility complex (MHC) genetics in northern pig-tailed macaques remains poorly understood. We have previously studied the MHC class I genes in northern pig-tailed macaques and identified 39 novel alleles. Here, we describe the MHC class II alleles in all six classical loci (DPA, DPB, DQA, DQB, DRA, and DRB) from northern pig-tailed macaques using a sequence-based typing method for the first time...
October 18, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/29046444/relative-resistance-of-mhc-b-to-nef-mediated-downregulation-is-conserved-among-primate-lentiviruses-and-influences-antiviral-t-cell-responses-in-hiv-1-infected-individuals
#7
Francis Mwimanzi, Mako Toyoda, Macdonald Mahiti, Jaclyn K Mann, Jeffrey N Martin, David Bangsberg, Mark A Brockman, Philip Goulder, Frank Kirchhoff, Zabrina L Brumme, Thumbi Ndung'u, Takamasa Ueno
Patient-derived HIV-1 subtype B Nef clones downregulate HLA-A more efficiently than HLA-B. However, it remains unknown whether this property is common to Nef proteins across primate lentiviruses, and how antiviral immune responses may be affected. We examined 263 Nef clones from diverse primate lentiviruses including different pandemic HIV-1 group M subtypes for their ability to downregulate MHC-A and MHC-B from the cell surface. Though lentiviral Nef proteins differed markedly in their absolute MHC-A and MHC-B downregulation abilities, all lentiviral Nef lineages downregulated MHC-A on average 11-32% more efficiently than MHC-B...
October 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29030661/identification-of-the-major-histocompatibility-complex-class-ii-dm-and-do-alleles-in-a-cohort-of-northern-pig-tailed-macaques-macaca-leonina
#8
Xiao-Dong Lian, Xi-He Zhang, Zheng-Xi Dai, Yong-Tang Zheng
The northern pig-tailed macaque (Macaca leonina) has been considered as an independent species from the pig-tailed macaque group. We have previously reported that this species macaque has the potential to be a useful animal model in HIV/AIDS pathogenesis and vaccine studies due to its susceptibility to HIV-1. To develop this animal into a potential HIV/AIDS model, we have studied the classical MHC genes of this animal. In this study, the non-classical MHC genes Malo-DM and Malo-DO alleles were first characterized by sequencing and cloning in 12 unrelated northern pig-tailed macaques...
October 13, 2017: Immunogenetics
https://www.readbyqxmd.com/read/29023371/expression-profiles-of-ligands-for-activating-natural-killer-cell-receptors-on-hiv-infected-and-uninfected-cd4%C3%A2-%C2%BA-t-cells
#9
Alexandra Tremblay-McLean, Julie Bruneau, Bertrand Lebouché, Irene Lisovsky, Rujun Song, Nicole F Bernard
Natural Killer (NK) cell responses to HIV-infected CD4 T cells (iCD4) depend on the integration of signals received through inhibitory (iNKR) and activating NK receptors (aNKR). iCD4 activate NK cells to inhibit HIV replication. HIV infection-dependent changes in the human leukocyte antigen (HLA) ligands for iNKR on iCD4 are well documented. By contrast, less is known regarding the HIV infection related changes in ligands for aNKR on iCD4. We examined the aNKR ligand profiles HIV p24⁺ HIV iCD4s that maintained cell surface CD4 (iCD4⁺), did not maintain CD4 (iCD4(-)) and uninfected CD4 (unCD4) T cells for expression of unique long (UL)-16 binding proteins-1 (ULBP-1), ULBP-2/5/6, ULBP-3, major histocompatibility complex (MHC) class 1-related (MIC)-A, MIC-B, CD48, CD80, CD86, CD112, CD155, Intercellular adhesion molecule (ICAM)-1, ICAM-2, HLA-E, HLA-F, HLA-A2, HLA-C, and the ligands to NKp30, NKp44, NKp46, and killer immunoglobulin-like receptor 3DS1 (KIR3DS1) by flow cytometry on CD4 T cells from 17 HIV-1 seronegative donors activated and infected with HIV...
October 12, 2017: Viruses
https://www.readbyqxmd.com/read/29021373/a-specialist-macaque-mhc-class-i-molecule-with-hla-b-27-like-peptide-binding-characteristics
#10
Natasja G de Groot, Corrine M C Heijmans, Arnoud H de Ru, George M C Janssen, Jan W Drijfhout, Nel Otting, Christelle Vangenot, Gaby G M Doxiadis, Frits Koning, Peter A van Veelen, Ronald E Bontrop
In different macaque species, the MHC A2*05 gene is present in abundance, and its gene products are characterized by low cell-surface expression and a highly conserved peptide-binding cleft. We have characterized the peptide-binding motif of Mamu-A2*05:01, and elucidated the binding capacity for virus-derived peptides. The macaque A2*05 allotype prefers the basic amino acid arginine at the second position of the peptide, and hydrophobic and polar amino acids at the C-terminal end. These preferences are shared with HLA-B*27 and Mamu-B*008, molecules shown to be involved in elite control in human HIV type 1 and macaque SIV infections, respectively...
October 11, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28993513/dna-vaccination-by-electroporation-amplifies-broadly-cross-restricted-public-tcr-clonotypes-shared-with-hiv-controllers
#11
Madhura Mukhopadhyay, Moran Galperin, Mandar Patgaonkar, Sandhya Vasan, David D Ho, Alexandre Nouël, Mathieu Claireaux, Daniela Benati, Olivier Lambotte, Yaoxing Huang, Lisa A Chakrabarti
Rare patients who spontaneously control HIV replication provide a useful model to inform HIV vaccine development. HIV controllers develop particularly efficient antiviral CD4(+) T cell responses mediated by shared high-affinity TCRs. To determine whether the candidate DNA vaccine ADVAX could induce similar responses, we analyzed Gag-specific primary CD4(+) T cells from healthy volunteers who received ADVAX DNA by electroporation. Vaccinated volunteers had an immunodominant response to the Gag293 epitope with a functional avidity intermediate between that of controllers and treated patients...
November 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28977405/genome-scale-detection-of-positive-selection-in-nine-primates-predicts-human-virus-evolutionary-conflicts
#12
Robin van der Lee, Laurens Wiel, Teunis J P van Dam, Martijn A Huynen
Hotspots of rapid genome evolution hold clues about human adaptation. We present a comparative analysis of nine whole-genome sequenced primates to identify high-confidence targets of positive selection. We find strong statistical evidence for positive selection in 331 protein-coding genes (3%), pinpointing 934 adaptively evolving codons (0.014%). Our new procedure is stringent and reveals substantial artefacts (20% of initial predictions) that have inflated previous estimates. The final 331 positively selected genes (PSG) are strongly enriched for innate and adaptive immunity, secreted and cell membrane proteins (e...
October 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28968755/evaluating-the-impact-of-functional-genetic-variation-on-hiv-1-control
#13
Paul J McLaren, Sara L Pulit, Deepti Gurdasani, Istvan Bartha, Patrick R Shea, Cristina Pomilla, Namrata Gupta, Effrossyni Gkrania-Klotsas, Elizabeth H Young, Norbert Bannert, Julia Del Amo, John Gill, Jill Gilmour, Paul Kellam, Anthony D Kelleher, Anders Sönnerborg, Robert Zangerle, Frank A Post, Martin Fisher, David W Haas, Bruce D Walker, Kholoud Porter, David B Goldstein, Manjinder S Sandhu, Paul I W de Bakker, Jacques Fellay
Background: Previous genetic association studies of HIV-1 progression have focused on common human genetic variation ascertained through genome-wide genotyping. Methods: We sought to systematically assess the full spectrum of functional variation in protein coding gene regions on HIV-1 progression through exome sequencing of 1,327 individuals. Genetic variants were tested individually and in aggregate across genes and gene sets for an influence on HIV-1 viral load...
September 9, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28934310/sanger-and-next-generation-sequencing-data-for-characterization-of-ctl-epitopes-in-archived-hiv-1-proviral-dna
#14
Camille Tumiotto, Lionel Riviere, Pantxika Bellecave, Patricia Recordon-Pinson, Alice Vilain-Parce, Gwenda-Line Guidicelli, Hervé Fleury
One of the strategies for curing viral HIV-1 is a therapeutic vaccine involving the stimulation of cytotoxic CD8-positive T cells (CTL) that are Human Leucocyte Antigen (HLA)-restricted. The lack of efficiency of previous vaccination strategies may have been due to the immunogenic peptides used, which could be different from a patient's virus epitopes and lead to a poor CTL response. To counteract this lack of specificity, conserved epitopes must be targeted. One alternative is to gather as many data as possible from a large number of patients on their HIV-1 proviral archived epitope variants, taking into account their genetic background to select the best presented CTL epitopes...
2017: PloS One
https://www.readbyqxmd.com/read/28931083/in-vivo-virulence-of-mhc-adapted-aids-virus-serially-passaged-through-mhc-mismatched-hosts
#15
Sayuri Seki, Takushi Nomura, Masako Nishizawa, Hiroyuki Yamamoto, Hiroshi Ishii, Saori Matsuoka, Teiichiro Shiino, Hironori Sato, Kazuta Mizuta, Hiromi Sakawaki, Tomoyuki Miura, Taeko K Naruse, Akinori Kimura, Tetsuro Matano
CD8+ T-cell responses exert strong suppressive pressure on HIV replication and select for viral escape mutations. Some of these major histocompatibility complex class I (MHC-I)-associated mutations result in reduction of in vitro viral replicative capacity. While these mutations can revert after viral transmission to MHC-I-disparate hosts, recent studies have suggested that these MHC-I-associated mutations accumulate in populations and make viruses less pathogenic in vitro. Here, we directly show an increase in the in vivo virulence of an MHC-I-adapted virus serially-passaged through MHC-I-mismatched hosts in a macaque AIDS model despite a reduction in in vitro viral fitness...
September 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28893294/hiv-i-nef-inhibitors-a-novel-class-of-hiv-specific-immune-adjuvants-in-support-of-a-cure
#16
REVIEW
Gregory A Dekaban, Jimmy D Dikeakos
The success of many current vaccines relies on a formulation that incorporates an immune activating adjuvant. This will hold true for the design of a successful therapeutic HIV vaccine targeted at controlling reactivated virus following cessation of combined antiretroviral therapy (cART). The HIV accessory protein Nef functions by interfering with HIV antigen presentation through the major histocompatibility complex I (MHC-I) pathway thereby suppressing CD8(+) cytotoxic T cell (CTL)-mediated killing of HIV infected cells...
September 12, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28893287/natural-killer-nk-cell-receptor-hla-ligand-genotype-combinations-associated-with-protection-from-hiv-infection-investigation-of-how-protective-genotypes-influence-anti-hiv-nk-cell-functions
#17
REVIEW
Nicole F Bernard
The anti-HIV activity of natural killer (NK) cells could be induced fast enough to potentially prevent the establishment of HIV infection. Epidemiological studies identified two genotypes encoding NK receptors that contribute to NK cell function, that were more frequent in people who remained uninfected despite multiple HIV exposures than in HIV-susceptible subjects. NK cells from carriers of the *h/*y+B*57 genotype have higher NK cell functional potential and inhibit HIV replication in autologous HIV-infected CD4+ T cells (iCD4) more potently than those from carriers of non-protective genotypes...
September 12, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28878119/pharmacologic-hiv-1-nef-blockade-promotes-cd8-t-cell-mediated-elimination-of-latently-hiv-1-infected-cells-in-vitro
#18
Shariq Mujib, Aamir Saiyed, Saleh Fadel, Ardalan Bozorgzad, Nasra Aidarus, Feng Yun Yue, Erika Benko, Colin Kovacs, Lori A Emert-Sedlak, Thomas E Smithgall, Mario A Ostrowski
Eradication of the HIV-1 latent reservoir represents the current paradigm to developing a cure for AIDS. HIV-1 has evolved multiple mechanisms to evade CD8 T cell responses, including HIV-1 Nef-mediated downregulation of MHC-I from the surface of infected cells. Nef transcripts and protein are detectable in samples from aviremic donors, suggesting that Nef expression in latently HIV-1-infected CD4 T cells protects them from immune-mediated clearance. Here, we tested 4 small molecule inhibitors of HIV-1 Nef in an in vitro primary CD4 T cell latency model and measured the ability of autologous ex vivo or HIV-1 peptide-expanded CD8 T cells to recognize and kill latently infected cells as a function of inhibitor treatment...
September 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/28861087/alanine-mutagenesis-in-the-complementarity-determining-region-3-of-the-mtb-and-hiv-1-peptide-bispecific-t-cell-receptor-beta-chain-affects-ligand-recognition
#19
Chao-Ying Zhou, Rui-Ning Wang, Qian Wen, Wen-Ting He, Shi-Meng Zhang, Xia-Lin Du, Jia-Hui Yang, Li Ma
Mycobacterium tuberculosis/human immunodeficiency virus (MTB/HIV) coinfection presents a special challenge to the prevention and treatment of tuberculosis and HIV/AIDS. Adoptive transfer of high-affinity T cell receptor (TCR) gene-modified T cells against MTB and HIV antigens is a promising approach to treating MTB/HIV coinfected patients whose cellular immunity is obviously disordered. We have previously successfully identified that a bispecific TCR screened out from peripheral blood mononuclear cells of a HLA-A*0201(+) healthy individual using the complementarity determining region 3 (CDR3) spectratype analysis recognizes both MTB Ag85B199-207 and HIV-1 Env120-128 peptide...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28805676/inhibitors-of-deubiquitinating-enzymes-block-hiv-1-replication-and-augment-the-presentation-of-gag-derived-mhc-i-epitopes
#20
Christian Setz, Melanie Friedrich, Pia Rauch, Kirsten Fraedrich, Alina Matthaei, Maximilian Traxdorf, Ulrich Schubert
In recent years it has been well established that two major constituent parts of the ubiquitin proteasome system (UPS)-the proteasome holoenzymes and a number of ubiquitin ligases-play a crucial role, not only in virus replication but also in the regulation of the immunogenicity of human immunodeficiency virus type 1 (HIV-1). However, the role in HIV-1 replication of the third major component, the deubiquitinating enzymes (DUBs), has remained largely unknown. In this study, we show that the DUB-inhibitors (DIs) P22077 and PR-619, specific for the DUBs USP7 and USP47, impair Gag processing and thereby reduce the infectivity of released virions without affecting viral protease activity...
August 12, 2017: Viruses
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