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https://www.readbyqxmd.com/read/28893294/hiv-i-nef-inhibitors-a-novel-class-of-hiv-specific-immune-adjuvants-in-support-of-a-cure
#1
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
#2
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
#3
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
#4
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
#5
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
https://www.readbyqxmd.com/read/28794233/characterization-of-mycobacterium-tuberculosis-specific-cells-using-mhc-class-ii-tetramers-reveals-phenotypic-differences-related-to-hiv-infection-and-tuberculosis-disease
#6
Natalie Strickland, Tracey L Müller, Natacha Berkowitz, Rene Goliath, Mary N Carrington, Robert J Wilkinson, Wendy A Burgers, Catherine Riou
A major challenge for the development of an effective vaccine against tuberculosis (TB) is that the attributes of protective CD4(+) T cell responses are still elusive for human TB. Infection with HIV type 1 is a major risk factor for TB, and a better understanding of HIV-induced alterations of Mycobacterium tuberculosis-specific CD4(+) T cells that leads to failed host resistance may provide insight into protective T cell immunity to TB. A total of 86 participants from a TB-endemic setting, either HIV-infected or uninfected and with latent or active TB (aTB), were screened using M...
August 9, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28772259/high-frequency-of-human-leukocyte-antigen-b-57-01-allele-carriers-among-hiv-infected-patients-in-serbia
#7
Marina Siljic, Dubravka Salemovic, Valentina Cirkovic, Ivana Pesic-Pavlovic, Marija Todorovic, Jovan Ranin, Gordana Dragovic, Djordje Jevtovic, Maja Stanojevic
Abacavir is an effective antiretroviral drug and one of the most commonly used nucleoside reverse transcriptase inhibitors in Serbia. А percentage of the treated patients experience a potentially life-threatening hypersensitivity reaction, which was shown to be associated with the presence of the class I MHC allele, HLA-B*57:01; hence genotyping for HLA-B*57:01 prior to starting abacavir is nowadays recommended in international HIV treatment guidelines. In Serbia, this testing became available in 2013. This study was designed to estimate the prevalence of the HLA-B*57:01 allele in Serbian HIV-1-infected patients...
August 4, 2017: Intervirology
https://www.readbyqxmd.com/read/28755872/new-approaches-for-the-enhancement-of-chimeric-antigen-receptors-for-the-treatment-of-hiv
#8
REVIEW
Mayra A Carrillo, Anjie Zhen, Jerome A Zack, Scott G Kitchen
HIV infection continues to be a life-long chronic disease in spite of the success of antiretroviral therapy (ART) in controlling viral replication and preventing disease progression. However, because of the high cost of treatment, severe side effects, and inefficiency in curing the disease with ART, there is a call for alternative therapies that will provide a functional cure for HIV. Cytotoxic T lymphocytes (CTLs) are vital in the control and clearance of viral infections and therefore immune-based therapies have attempted to engineer HIV-specific CTLs that would be able to clear the infection from the body...
September 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28748659/mauritian-cynomolgus-macaques-with-m3m4-mhc-genotype-control-sivmac251-infection
#9
Hongzhao Li, Robert W Omange, Chris Czarnecki, Jorge F Correia-Pinto, Jose Crecente-Campo, Meika Richmond, Lin Li, Nancy Schultz-Darken, Maria J Alonso, James B Whitney, Francis A Plummer, Ma Luo
BACKGROUND: Understanding natural HIV control may lead to new preventative or therapeutic strategies. Several protective major histocompatibility complex (MHC) genotypes were found in humans and rhesus macaques. Here, we report a simian immunodeficiency virus (SIV) controller MHC genotype in Mauritian cynomolgus macaques (MCMs). METHODS: Twelve MHC-genotyped MCMs were infected with SIVmac251 and monitored for viral loads and CD4+ T-cell counts. RESULTS: Two macaques with M3M4 genotype exhibited the lowest peak viral loads (log plasma SIV RNA copies/mL), nearly 3 logs lower than those in most macaques with other MHC haplotype combinations, and set point viral loads below the level of detection limit by RT-qPCR (<2 log RNA copies/mL)...
August 2017: Journal of Medical Primatology
https://www.readbyqxmd.com/read/28743825/contribution-of-the-clathrin-adaptor-ap-1-subunit-%C3%A2%C2%B51-to-acidic-cluster-protein-sorting
#10
Paloma Navarro Negredo, James R Edgar, Antoni G Wrobel, Nathan R Zaccai, Robin Antrobus, David J Owen, Margaret S Robinson
Acidic clusters act as sorting signals for packaging cargo into clathrin-coated vesicles (CCVs), and also facilitate down-regulation of MHC-I by HIV-1 Nef. To find acidic cluster sorting machinery, we performed a gene-trap screen and identified the medium subunit (µ1) of the clathrin adaptor AP-1 as a top hit. In µ1 knockout cells, intracellular CCVs still form, but acidic cluster proteins are depleted, although several other CCV components were either unaffected or increased, indicating that cells can compensate for long-term loss of AP-1...
September 4, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28738755/qsar-dft-and-molecular-modeling-studies-of-peptides-from-hiv-1-to-describe-their-recognition-properties-by-mhc-i
#11
S Andrade-Ochoa, J García-Machorro, Martiniano Bello, L M Rodríguez-Valdez, C A Flores-Sandoval, J Correa-Basurto
Human immunodeficiency virus type-1 (HIV-1) has infected more than 40 million people around the world. HIV-1 treatment still has several side effects, and the development of a vaccine, which is another potential option for decreasing human infections, has faced challenges. This work presents a computational study that includes a quantitative structure activity relationship (QSAR) using density functional theory for reported peptides to identify the principal quantum mechanics descriptors related to peptide activity...
July 25, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28696158/immunization-with-hiv-1-envelope-t20-encoding-dna-vaccines-elicits-cross-clade-neutralizing-antibody-responses
#12
S Stenler, K E Lundin, L Hansen, S Petkov, N Mozafari, M Isaguliants, P Blomberg, C I E Smith, D M Goldenberg, C-H Chang, K Ljungberg, J Hinkula, B Wahren
BACKGROUND: Genetic immunization is expected to induce the expression of antigens in a native form. The encoded peptide epitopes are presented on endogenous MHC molecules, mimicking antigen presentation during a viral infection. We have explored the potential of enfuvirtide (T20), a short HIV peptide with antiviral properties, to enhance immune response to HIV antigens. To generate an expression vector, the T20 sequence was cloned into a conventional plasmid, the novel minicircle construct, and a replicon plasmid...
July 11, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28695289/the-role-of-mhc-class-i-gene-products-in-siv-infection-of-macaques
#13
REVIEW
Zachary A Silver, David I Watkins
Human immunodeficiency virus (HIV) remains among the most significant public health threats worldwide. Despite three decades of research following the discovery of HIV, a preventive vaccine remains elusive. The study of HIV elite controllers has been crucial to elaborate the genetic and immunologic determinants that underlie control of HIV replication. Coordinated studies of elite control in humans have, however, been limited by variability among infecting viral strains, host genotype, and the uncertainty of the timing and route of infection...
July 10, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28695283/aids-in-chimpanzees-the-role-of-mhc-genes
#14
REVIEW
Natasja G de Groot, Corinne M C Heijmans, Ronald E Bontrop
The ancestral progenitor of common chimpanzees and bonobos experienced a selective sweep that ravaged its major histocompatibility complex (MHC) class I repertoire. The causative agent was probably an ancestral retrovirus, highly related to the contemporary HIV-1 strain, which initiated the acquired immunodeficiency syndrome pandemic in the human population. As a direct result, MHC class I allotypes with the capability of targeting conserved retroviral elements were enriched in the ancestral progenitor. Even today, the impact can be traced back by studying the functional capacities of the contemporary MHC class I allotypes of common chimpanzees...
July 10, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28667761/persistent-accumulation-of-gut-macrophages-with-impaired-phagocytic-function-correlates-with-siv-disease-progression-in-macaques
#15
Zachary D Swan, Anthea L Bouwer, Elizabeth R Wonderlich, Simon M Barratt-Boyes
The contribution of macrophages in the gastrointestinal tract to disease control or progression in HIV infection remains unclear. To address this question, we analyzed CD163(+) macrophages in ileum and mesenteric lymph nodes (LN) from SIV-infected rhesus macaques with dichotomous expression of controlling MHC class I alleles predicted to be SIV controllers or progressors. Infection induced accumulation of macrophages into gut mucosa in the acute phase that persisted in progressors but was resolved in controllers...
July 1, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28654687/combined-single-cell-quantitation-of-host-and-siv-genes-and-proteins-ex-vivo-reveals-host-pathogen-interactions-in-individual-cells
#16
Diane L Bolton, Kathleen McGinnis, Greg Finak, Pratip Chattopadhyay, Raphael Gottardo, Mario Roederer
CD4 T cells harboring HIV-1/SIV represent a formidable hurdle to eradicating infection, and yet their detailed phenotype remains unknown. Here we integrate two single-cell technologies, flow cytometry and highly multiplexed quantitative RT-PCR, to characterize SIV-infected CD4 T cells directly ex vivo. Within individual cells, we correlate the cellular phenotype, in terms of host protein and RNA expression, with stages of the viral life cycle defined by combinatorial expression of viral RNAs. Spliced RNA+ infected cells display multiple memory and activation phenotypes, indicating virus production by diverse CD4 T cell subsets...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28649242/an-approach-for-a-synthetic-ctl-vaccine-design-against-zika-flavivirus-using-class-i-and-class-ii-epitopes-identified-by-computer-modeling
#17
Edecio Cunha-Neto, Daniela S Rosa, Paul E Harris, Tim Olson, Alex Morrow, Serban Ciotlos, Charles V Herst, Reid Martin Rubsamen
The threat posed by severe congenital abnormalities related to Zika virus (ZKV) infection during pregnancy has turned development of a ZKV vaccine into an emergency. Recent work suggests that the cytotoxic T lymphocyte (CTL) response to infection is an important defense mechanism in response to ZKV. Here, we develop the rationale and strategy for a new approach to developing cytotoxic T lymphocyte (CTL) vaccines for ZKV flavivirus infection. The proposed approach is based on recent studies using a protein structure computer model for HIV epitope selection designed to select epitopes for CTL attack optimized for viruses that exhibit antigenic drift...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28615212/conserved-v%C3%AE-1-binding-geometry-in-a-setting-of-locus-disparate-phla-recognition-by-%C3%AE-%C3%AE-%C3%AE-tcrs-insight-into-recognition-of-hiv-peptides-by-tcr
#18
Yi Shi, Ai Kawana-Tachikawa, Feng Gao, Jianxun Qi, Chuansheng Liu, Jia Gao, Hao Cheng, Takamasa Ueno, Aikichi Iwamoto, George F Gao
Given a limited set of TCR V genes which are used to create TCRs that are reactive to different ligands, such as MHC class I, MHC class II and MHC-like proteins (for example, MIC molecules and CD1 molecules), the Vδ1 segment can be rearranged with Dδ-Jδ-Cδ or Jα-Cα segments, to form classical γδTCR or uncommon αβTCR using a Vδ1 segment (δ/αβTCR). Here we have determined two complex structures of the δ/αβTCRs (S19-2 and TU55) bound to different locus-disparate MHCIs with HIV peptides (HLA-A*2402-Nef138-10 and HLA-B*3501-Pol448-9)...
June 14, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28544366/enumeration-of-wt1-specific-cd8-t-cells-for-clinical-application-using-an-mhc-streptamer-based-no-wash-single-platform-flow-cytometric-assay
#19
Sarah Matko, Madeleine Teichert, Antje Tunger, Marc Schmitz, Martin Bornhauser, Torsten Tonn, Marcus Odendahl
The advent of novel strategies to generate leukemia-associated-antigen (LAA)-specific T cells for adoptive immunotherapies creates a demand for standardized good laboratory practice (GLP)-compliant enumeration assays to provide a secure clinical environment-whether it is to identify potential donors, define therapeutic doses for transplantation, or monitor clinical success. Here, we introduce a no-wash assay based on single-platform cell enumeration and Streptamer staining to determine the Wilms' tumor antigen 1 (WT1)-specific T cell immunity in clinical samples...
May 25, 2017: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
https://www.readbyqxmd.com/read/28505602/unusual-antigen-presentation-offers-new-insight-into-hiv-vaccine-design
#20
REVIEW
Andrew J McMichael, Louis J Picker
Recent findings with a rhesus monkey cytomegalovirus based simian immunodeficiency virus vaccine have identified strong CD8+ T cell responses that are restricted by MHC-E. Also mycobacteria specific CD8+ T cells, that are MHC-E restricted, have been identified. MHC-E therefore can present a wide range of epitope peptides to CD8+ T cells, alongside its well defined role in presenting a conserved MHC-class I signal peptide to the NKG2A/C-CD94 receptor on natural killer cells. Here we explore the antigen processing pathways involved in these atypical T cell responses...
June 2017: Current Opinion in Immunology
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