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https://www.readbyqxmd.com/read/28931520/dna-priming-increases-frequency-of-t-cell-responses-to-a-vsv-hiv-vaccine-with-specific-enhancement-of-cd8-t-cell-responses-by-il-12-pdna
#1
Shuying S Li, Nidhi K Kochar, Marnie Elizaga, Christine M Hay, Gregory J Wilson, Kristen W Cohen, Stephen C De Rosa, Rong Xu, Ayuko Ota-Setlik, Daryl Morris, Greg Finak, Mary Allen, Hong-Van Tieu, Ian Frank, Magdalena E Sobieszczyk, Drew Hannaman, Raphael Gottardo, Peter B Gilbert, Georgia D Tomaras, Lawrence Corey, David K Clarke, Michael A Egan, John H Eldridge, M Juliana McElrath, Nicole Frahm
HVTN 087 assessed the effect of increasing doses of pIL-12 adjuvant on the immunogenicity of a HIV-1 multi-antigen (MAG) DNA vaccine delivered by electroporation and boosted with an attenuated VSV-Gag vaccine. We randomized 100 healthy adults to receive placebo, or 3mg HIV-MAG (gag/pol, env, nef/tat/vif) DNA vaccine co-administered with pIL-12 at 0μg, 250μg, 1,000μg or 1,500μg intramuscularly by electroporation at 0, 1 and 3 months followed by intramuscular inoculation with 3.4×10(7) PFU VSV-Gag vaccine at 6 months...
September 20, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28931091/mt-cell-responses-targeting-hiv-nef-uniquely-correlate-with-infected-cell-frequencies-after-long-term-antiretroviral-therapy
#2
Allison S Thomas, Kimberley L Jones, Rajesh T Gandhi, Deborah K McMahon, Joshua C Cyktor, Dora Chan, Szu-Han Huang, Ronald Truong, Alberto Bosque, Amanda B Macedo, Colin Kovacs, Erika Benko, Joseph J Eron, Ronald J Bosch, Christina M Lalama, Samuel Simmens, Bruce D Walker, John W Mellors, R Brad Jones
HIV-specific CD8+ T-cell responses limit viral replication in untreated infection. After the initiation of antiretroviral therapy (ART), these responses decay and the infected cell population that remains is commonly considered to be invisible to T-cells. We hypothesized that HIV antigen recognition may persist in ART-treated individuals due to low-level or episodic protein expression. We posited that if persistent recognition were occurring it would be preferentially directed against the early HIV gene products Nef, Tat, and Rev as compared to late gene products, such as Gag, Pol, and Env, which have higher barriers to expression...
September 20, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28917624/small-heat-shock-protein-27-an-effective-adjuvant-for-enhancement-of-hiv-1-nef-antigen-specific-immunity
#3
Alireza Milani, Azam Bolhassani, Sepideh Shahbazi, Fatemeh Motevalli, Seyed Mehdi Sadat, Sepehr Soleymani
Novel vaccine modalities have been designed to improve the efficiency of vaccines against HIV infections. In this way, the HIV-1 Nef protein has been known as an attractive antigenic candidate in therapeutic vaccine development. Moreover, the endogenous adjuvants such as heat shock proteins (HSPs) and high mobility group box 1 protein (HMGB1) have been suggested effectively to induce antigen-specific humoral and cellular immune responses. In this study, different Nef DNA and protein constructs were produced in eukaryotic and prokaryotic expression systems, and their immunostimulatory properties were evaluated using small heat shock protein 27 (Hsp27) and the HMGB1-derived peptide (Hp91) in a mouse model...
September 13, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28911170/sertoli-cell-number-defines-and-predicts-germ-and-leydig-cell-population-sizes-in-the-adult-mouse-testis
#4
Diane Rebourcet, Annalucia Darbey, Ana Monteiro, Ugo Soffientini, Yi Ting Tsai, Ian Handel, Jean-Luc Pitetti, Serge Nef, Lee B Smith, Peter J O'Shaughnessy
Sertoli cells regulate differentiation and development of the testis and are essential for maintaining adult testis function. To model the effects of dysregulating Sertoli cell number during development or aging, we have used acute diphtheria toxin-mediated cell ablation to reduce Sertoli cell population size. Results show that the size of the Sertoli cell population that forms during development determines the number of germ cells and Leydig cells that will be present in the adult testis. Similarly, the number of germ cells and Leydig cells that can be maintained in the adult depends directly on the size of the adult Sertoli cell population...
September 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28893294/hiv-i-nef-inhibitors-a-novel-class-of-hiv-specific-immune-adjuvants-in-support-of-a-cure
#5
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/28893272/killed-whole-hiv-vaccine-employing-a-well-established-strategy-for-antiviral-vaccines
#6
REVIEW
C Yong Kang, Yong Gao
The development of an efficient prophylactic HIV vaccine has been one of the major challenges in infectious disease research during the last three decades. Here, we present a mini review on strategies employed for the development of HIV vaccines with an emphasis on a well-established vaccine technology, the killed whole-virus vaccine approach. Recently, we reported an evaluation of the safety and the immunogenicity of a genetically modified and killed whole-HIV-1 vaccine designated as SAV001 [1]. HIV-1 Clade B NL4-3 was genetically modified by deleting the nef and vpu genes and substituting the coding sequence of the Env signal peptide with that of honeybee melittin to produce an avirulent and replication efficient HIV-1...
September 12, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28885709/prenylation-of-viral-proteins-by-enzymes-of-the-host-virus-driven-rationale-for-therapy-with-statins-and-ft-ggt1-inhibitors
#7
REVIEW
Ekaterina S Marakasova, Birgit Eisenhaber, Sebastian Maurer-Stroh, Frank Eisenhaber, Ancha Baranova
Intracellular bacteria were recently shown to employ eukaryotic prenylation system for modifying activity and ensuring proper intracellular localization of their own proteins. Following the same logic, the proteins of viruses may also serve as prenylation substrates. Using extensively validated high-confidence prenylation predictions by PrePS with a cut-off for experimentally confirmed farnesylation of hepatitis delta virus antigen, we compiled in silico evidence for several new prenylation candidates, including IRL9 (CMV) and few other proteins encoded by Herpesviridae, Nef (HIV-1), E1A (human adenovirus 1), NS5A (HCV), PB2 (influenza), HN (human parainfluenza virus 3), L83L (African swine fever), MC155R (molluscum contagiosum virus), other Poxviridae proteins, and some bacteriophages of human associated bacteria...
September 8, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28882621/antibodies-targeting-btla-or-tim-3-enhance-hiv-1-specific-t-cell-responses-in-combination-with-pd-1-blockade
#8
Katharina Grabmeier-Pfistershammer, Carmen Stecher, Markus Zettl, Sandra Rosskopf, Armin Rieger, Gerhard J Zlabinger, Peter Steinberger
Persistent stimulation with antigens derived from viruses that establish chronic infections or tumour antigens results in the exhaustion of T cells. Coinhibitory receptors like PD-1 and CTLA-4 function as immune checkpoints on exhausted T cells. Blocking these molecules with antibodies improve immunity to cancer cells. Immune checkpoint inhibitors targeting other coinhibitory receptors might have a similar role in improving T cell function and thus also utility in cancer therapy. Using HIV-specific T cells as a model for exhaustion we have evaluated the capacity of antibodies targeting TIM-3, BTLA, CD160, LAG-3 and CTLA-4 alone or in combination with a PD-1 antibody to enhance proliferation and cytokine production in response to Gag and Nef peptides...
September 4, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
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
#9
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/28874665/endocytic-sorting-motif-interactions-involved-in-nef-mediated-downmodulation-of-cd4-and-cd3
#10
Santiago Manrique, Daniel Sauter, Florian A Horenkamp, Sebastian Lülf, Hangxing Yu, Dominik Hotter, Kanchan Anand, Frank Kirchhoff, Matthias Geyer
Lentiviral Nefs recruit assembly polypeptide complexes and target sorting motifs in cellular receptors to induce their internalization. While Nef-mediated CD4 downmodulation is conserved, the ability to internalize CD3 was lost in HIV-1 and its precursors. Although both functions play key roles in lentiviral replication and pathogenicity, the underlying structural requirements are poorly defined. Here, we determine the structure of SIVmac239 Nef bound to the ExxxLM motif of another Nef molecule at 2.5 Å resolution...
September 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/28870874/characteristics-and-outcome-following-transcatheter-aortic-valve-replacement-of-patients-with-severe-aortic-stenosis-with-low-flow
#11
Yigal Abramowitz, Tarun Chakravarty, Philippe Pibarot, Yoshio Maeno, Hiroyuki Kawamori, David Anderson, Geeteshwar Mangat, Mamoo Nakamura, Wen Cheng, Raj R Makkar
AIMS: Only few studies examined the respective impact of low flow (LF), low gradient (LG) and low ejection fraction (LEF) on outcomes following transcatheter aortic valve replacement (TAVR). The purpose of this study was to assess the impact of pre-procedural stroke volume index, aortic valve gradient, left ventricular ejection fraction (LVEF) and different flow/gradient/LVEF patterns on the clinical outcomes of patients with severe aortic stenosis (AS) that undergo TAVR. METHODS AND RESULTS: We analyzed the clinical, echocardiographic, and outcome data collected in 770 patients with AS that underwent TAVR...
September 5, 2017: EuroIntervention
https://www.readbyqxmd.com/read/28861036/contralesional-trunk-rotation-dissociates-real-vs-pseudo-visual-field-defects-due-to-visual-neglect-in-stroke-patients
#12
Thomas Nyffeler, Rebecca E Paladini, Simone Hopfner, Oliver Job, Tobias Nef, Tobias Pflugshaupt, Tim Vanbellingen, Stephan Bohlhalter, René M Müri, Georg Kerkhoff, Dario Cazzoli
In stroke patients, the clinical presentation of visual field defects (VFDs) is frequently accompanied by visual neglect, i.e., the inability to attend and respond to the contralesional space. However, the diagnostic discrimination between the lack of reactions to contralesional stimuli due to VFDs or visual neglect is challenging during clinical examination. This discrimination is particularly relevant, since both clinical pictures are associated with different therapeutic approaches and outcomes. The aim of this study was to systematically investigate the effectiveness of trunk rotation toward the contralesional side-a manipulation dissociating the coordinate system of the trunk from that of the head and eyes-in disentangling real VFDs from "pseudo-VFDs" that occur due to visual neglect...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28859166/primate-lentiviruses-use-at-least-three-alternative-strategies-to-suppress-nf-%C3%AE%C2%BAb-mediated-immune-activation
#13
Dominik Hotter, Teresa Krabbe, Elisabeth Reith, Ali Gawanbacht, Nadia Rahm, Ahidjo Ayouba, Benoît Van Driessche, Carine Van Lint, Martine Peeters, Frank Kirchhoff, Daniel Sauter
Primate lentiviruses have evolved sophisticated strategies to suppress the immune response of their host species. For example, HIV-2 and most simian immunodeficiency viruses (SIVs) use their accessory protein Nef to prevent T cell activation and antiviral gene expression by downmodulating the T cell receptor CD3. This Nef function was lost in HIV-1 and other vpu-encoding viruses suggesting that the acquisition of Vpu-mediated NF-κB inhibition reduced the selection pressure for inhibition of T cell activation by Nef...
August 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28832407/prevalence-and-clinical-impacts-of-hiv-1-intersubtype-recombinants-in-uganda-revealed-by-near-full-genome-population-and-deep-sequencing-approaches
#14
Guinevere Q Lee, David R Bangsberg, Theresa Mo, Chris Lachowski, Chanson J Brumme, Wendy Zhang, Viviane D Lima, Yap Boum, Bosco Bwana Mwebesa, Conrad Muzoora, Iren Andia, Yona Mbalibulha, Annet Kembabazi, Ryan Carroll, Mark J Siedner, Jessica E Haberer, A Rain Mocello, Simone H Kigozi, Peter W Hunt, Jeffrey N Martin, P Richard Harrigan
OBJECTIVES: To estimate prevalence, examine time trends, and test for clinical correlates and outcomes associated with HIV-1 intersubtype recombination under a full-genome sequencing context in a rural community in Mbarara, Uganda, where HIV-1 subtypes A1 and D co-circulate. METHODS: Near-full-genome HIV-1 Sanger sequence data was collected from plasma samples of 504 treatment-naïve individuals, who then received PI or NNRTI-containing regimens and were monitored for up to 7...
August 21, 2017: AIDS
https://www.readbyqxmd.com/read/28829745/everolimus-eluting-bioresorbable-scaffolds-in-patients-with-coronary-artery-disease-results-from-the-german-austrian-absorb-registry-gabi-r
#15
Holger M Nef, Jens Wiebe, Johannes Kastner, Julinda Mehilli, Thomas Münzel, Christoph Naber, Till Neumann, Gert Richardt, Axel Schmermund, Jochen Wöhrle, Ralf Zahn, Thomas Riemer, Stephan Achenbach, Christian W Hamm
AIMS: To analyze procedural results and mid-term safety of everolimus-eluting bioresorbable vascular scaffolds (BVS) used for percutaneous coronary intervention in a large all-comer cohort from the German-Austrian ABSORB Registry (GABI-R). METHODS AND RESULTS: A total of 3231 patients were included in this prospective, observational, multicentre study (Clinicaltrial.gov NCT02066623) of consecutive patients undergoing BVS implantation between November 2013 and January 2016...
August 22, 2017: EuroIntervention
https://www.readbyqxmd.com/read/28826900/identification-of-periprocedural-myocardial-infarction-using-a-high-sensitivity-troponin-i-assay-in-patients-who-underwent-transcatheter-aortic-valve-implantation
#16
Christoph Liebetrau, Won K Kim, Alexander Meyer, Mani Arsalan, Luise Gaede, Johannes M Blumenstein, Ulrich Fischer-Rasokat, Jan S Wolter, Oliver Dörr, Sandra Schillinger, Christian Troidl, Holger M Nef, Christian W Hamm, Thomas Walther, Helge Möllmann
Periprocedural myocardial infarction (MI), a rare complication after transcatheter aortic valve implantation (TAVI), is associated with worse outcome. According to the Valve Academic Research Consortium (VARC-2), MI is defined by an increase in cardiac troponin (cTn) and creatine kinase MB (CK-MB) levels; however, many patients show periprocedurally elevated cTn without clinical evidence of MI. The aims of this study were to establish reference values of cardiac troponin I measured with a high-sensitivity assay (hs-cTnI) and to assess the periprocedural diagnostic value of this biomarker in patients who underwent TAVI...
October 1, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28819214/hiv-1-nef-induced-cardiotoxicity-through-dysregulation-of-autophagy
#17
Manish K Gupta, Rafal Kaminski, Brian Mullen, Jennifer Gordon, Tricia H Burdo, Joseph Y Cheung, Arthur M Feldman, Muniswamy Madesh, Kamel Khalili
Cardiovascular disease is a leading cause of co-morbidity in HIV-1 positive patients, even those in whom plasma virus levels are well-controlled. The pathogenic mechanism of HIV-1-associated cardiomyopathy is unknown, but has been presumed to be mediated indirectly, owing to the absence of productive HIV-1 replication in cardiomyocytes. We sought to investigate the effect of the HIV-1 auxiliary protein, Nef, which is suspected of extracellular release by infected CD4+ T cells on protein quality control and autophagy in cardiomyocytes...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28793783/characterization-of-a-novel-hiv-1-second-generation-recombinant-form-in-men-who-have-sex-with-men-in-beijing-china
#18
Chen Wang, Yan Wang, Desheng Kong, Ruolei Xin, Weisi Xu, Yi Feng, Yiming Shao, Liying Ma
Cocirculation of multiple subtypes in the same population contributes significantly to the emergence of recombinant viruses. BJ2015EU19, a novel CCR5-tropic human immunodeficiency virus (HIV)-1, second-generation recombinant virus, was isolated from a man who has sex with men in Beijing, China. Phylogenetic analysis of the near full-length genome showed that BJ2015EU19 consisted of seven fragments from CRF01_AE and CRF07_BC. There were six recombinant breakpoints in the pol, vpu, env, and nef genes of BJ2015EU19, which were different from the other circulating recombinant forms and unique recombinant forms (URFs)...
September 8, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28783530/validation-of-the-who-5-as-a-first-step-screening-instrument-for-depression-in-adults-with-diabetes-results-from-diabetes-miles-australia
#19
Jennifer A Halliday, Christel Hendrieckx, Lucy Busija, Jessica L Browne, Giesje Nefs, François Pouwer, Jane Speight
AIMS: Screening for depression is recommended internationally. The World Health Organization's 5-item Well-being Index (WHO-5) is used clinically to screen for depression but its empirical suitability for this purpose is not well documented. We investigated the psychometric properties of the WHO-5 and its suitability for identifying likely depression in Australian adults with diabetes. METHODS: The Diabetes MILES - Australia study dataset provided a sample of N=3249 who completed the WHO-5 (positively-worded 5-item measure of emotional well-being) and the PHQ-9 (9-item measure of depressive symptoms)...
July 8, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28771107/hla-dqb1-06-and-breadth-of-nef-core-region-specific-t-cell-response-are-associated-with-slow-disease-progression-in-antiretroviral-therapy-naive-chinese-hiv-1-subtype-b-patients
#20
Weihua Li, Chuanyun Li, Wei Xia, Xiuhui Li
Vaccines still are an important way to prevent and treat acquired immunodeficiency syndrome (AIDS). (1) For developing an effective T cell-based AIDS vaccine, it is critical to define the human leukocyte antigen (HLA) type and epitope that elicit the most potent responses. This study involved 29 antiretroviral therapy-naive and chronic human immunodeficiency virus (HIV)-1 subtype B-infected individuals. A polymerase chain reaction-sequence-specific primer was used to detect the HLA typing, and the enzyme-linked immunospot assay to quantify the T-cell immune function...
August 3, 2017: Human Vaccines & Immunotherapeutics
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