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Virus specific t cells

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https://www.readbyqxmd.com/read/28650722/optimized-dna-vaccine-enhanced-by-adjuvant-il28b-induces-protective-immune-responses-against-herpes-simplex-virus-type-2-in-mice
#1
Yan Zhou, Ziyan Wang, Yongqing Xu, Zeqiang Zhang, Rui Hua, Wei Liu, Chunlai Jiang, Yan Chen, Wenying Yang, Wei Kong
Antigen-specific immune responses determine the efficacy of herpes simplex virus type 2 (HSV-2) vaccines. To optimize the immunogenicity of the antigen gD2, we developed the gD2ΔUL25 DNA vaccine encoding HSV-2 glycoprotein D and UL25 gene encoding viral capsid vertex proteins in this study. The gD2 and gD2ΔUL25 DNA vaccines were compared with formalin-inactivated HSV-2 (FI-HSV-2), and results showed a greater protective immune response induced by gD2ΔUL25 than by gD2. Therefore, gD2ΔUL25 was chosen to evaluate further using the IL28B adjuvant...
June 26, 2017: Viral Immunology
https://www.readbyqxmd.com/read/28650343/anthrax-toxin-receptor-1-is-the-cellular-receptor-for-seneca-valley-virus
#2
Linde A Miles, Laura N Burga, Eric E Gardner, Mihnea Bostina, John T Poirier, Charles M Rudin
Seneca Valley virus (SVV) is an oncolytic picornavirus with selective tropism for neuroendocrine cancers. It has shown promise as a cancer therapeutic in preclinical studies and early-phase clinical trials. Here, we have identified anthrax toxin receptor 1 (ANTXR1) as the receptor for SVV using genome-wide loss-of-function screens. ANTXR1 is necessary for permissivity in vitro and in vivo. However, robust SVV replication requires an additional innate immune defect. We found that SVV interacts directly and specifically with ANTXR1, that this interaction is required for SVV binding to permissive cells, and that ANTXR1 expression is necessary and sufficient for infection in cell lines with decreased expression of antiviral IFN genes at baseline...
June 26, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28650258/helper-t-cell-responses-to-respiratory-viruses-in-the-lung-development-virus-suppression-and-pathogenesis
#3
Kosuke Miyauchi
The lung is an important line of defense that is exposed to respiratory infectious pathogens, including viruses. Lung epithelial cells and/or alveolar macrophages are initially targeted by respiratory viruses. Once respiratory viruses invade the cells of the lung, innate immunity is activated to inhibit viral replication. Innate immune signaling also activates virus-specific adaptive immune responses. The helper T cells play pivotal roles in the humoral and cellular adaptive immune responses. Helper T cells are categorized into several distinct subsets (e...
June 26, 2017: Viral Immunology
https://www.readbyqxmd.com/read/28649380/gitr-ligand-fusion-protein-agonist-enhances-the-tumor-antigen-specific-cd8-t-cell-response-and-leads-to-long-lasting-memory
#4
Nick M Durham, Nick Holoweckyj, Randall S MacGill, Kelly McGlinchey, Ching Ching Leow, Scott H Robbins
BACKGROUND: The expansion of antigen-specific CD8 T cells is important in generating an effective and long-lasting immune response to tumors and viruses. Glucocorticoid-induced tumor necrosis factor receptor family-related receptor (GITR) is a co-stimulatory receptor that binds the GITR ligand (GITRL). Agonism of GITR can produce important signals that drive expansion of effector T cell populations. METHODS: We explored two separate murine tumor models, CT26 and TC-1, for responsiveness to GITR Ligand Fusion Protein(GITRL-FP) monotherapy...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28649246/redirected-primary-human-chimeric-antigen-receptor-natural-killer-cells-as-an-off-the-shelf-immunotherapy-for-improvement-in-cancer-treatment
#5
REVIEW
Olaf Oberschmidt, Stephan Kloess, Ulrike Koehl
Primary human natural killer (NK) cells recognize and subsequently eliminate virus infected cells, tumor cells, or other aberrant cells. However, cancer cells are able to develop tumor immune escape mechanisms to undermine this immune control. To overcome this obstacle, NK cells can be genetically modified to express chimeric antigen receptors (CARs) in order to improve specific recognition of cancer surface markers (e.g., CD19, CD20, and ErbB2). After target recognition, intracellular CAR domain signaling (CD3ζ, CD28, 4-1BB, and 2B4) leads to activation of PI3K or DNAX proteins (DAP10, DAP12) and finally to enhanced cytotoxicity, proliferation, and/or interferon γ release...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28648905/antibodies-against-immune-checkpoint-molecules-restore-functions-of-tumor-infiltrating-t-cells-in-hepatocellular-carcinomas
#6
Guoying Zhou, Dave Sprengers, Patrick P C Boor, Michail Doukas, Hannah Schutz, Shanta Mancham, Alexander Pedroza-Gonzalez, Wojciech G Polak, Jeroen de Jonge, Marcia Gaspersz, Haidong Dong, Kris Thielemans, Qiuwei Pan, Jan N M IJzermans, Marco J Bruno, Jaap Kwekkeboom
BACKGROUND & AIMS: Ligand binding to inhibitory receptors on immune cells, such as programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA4), downregulates the T-cell-mediated immune response (called immune checkpoints). Antibodies that block these receptors increase anti-tumor immunity in patients with melanoma, non-small cell lung cancer, and renal cell cancer. Tumor-infiltrating CD4(+) and CD8(+) T cells in patients with hepatocellular carcinoma (HCC) have been found to be functionally compromised...
June 22, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28647211/tubuloreticular-inclusions-in-peritubular-capillaries-of-renal-allografts
#7
Jee Youn Lee, Seung Hwan Song, Yu Seun Kim, Beom Jin Lim, Soon Il Kim, Myoung Soo Kim, Hyeon Joo Jeong
BACKGROUND: Tubuloreticular inclusions (TRIs) are anastomosing networks of microtubules that are frequently found in autoimmune diseases and viral infections. In renal allografts, TRIs have been reported in glomerular endothelial cells in association with viral infections and donor specific antibodies (DSAs), but their presence in peritubular capillaries has not been explored. METHODS: We collected seven cases with TRIs out of 148 consecutive renal allograft biopsies taken from Dec...
June 6, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28646491/sickle-cells-produce-functional-immune-modulators-and-cytotoxics
#8
Chiao-Wang Sun, Li-Chen Wu, Peter L Knopick, David S Bradley, Tim Townes, David S Terman
Sickle erythrocytes' (SSRBCs) unique physical adaptation to hypoxic conditions renders them able to home to hypoxic tumor niches in vivo, shut down tumor blood flow and induce tumoricidal responses. SSRBCs are also useful vehicles for transport of encapsulated drugs and oncolytic virus into hypoxic tumors with enhanced anti-tumor effects. In search of additional modes for arming sickle cells with cytotoxics, we turned to a lentiviral β-globin vector with optimized Locus Control Region/β-globin coding region/promoter/enhancers...
June 24, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28646236/rapamycin-adjuvant-and-exacerbation-of-severe-influenza-in-an-experimental-mouse-model
#9
Ching-Tai Huang, Chen-Yiu Hung, Tse-Ching Chen, Chun-Yen Lin, Yung-Chang Lin, Chia-Shiang Chang, Yueh-Chia He, Yu-Lin Huang, Avijit Dutta
Influenza virus infection often causes severe disease and acute respiratory distress syndrome. It is a common belief that overwhelming immune response contributes to the severe illness. Physicians and researchers have put forth immune modulation as salvage therapy for better recovery. However, empiric corticosteroid failed in both humans and animal models. Reported success with Rapamycin in humans prompted a comprehensive animal study and mechanistic dissection. Here we report the effect of Rapamycin alone or in combination with Oseltamivir for severe influenza in BALB/c mice...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646094/immune-mediated-effects-targeting-hepatitis-c-virus-in-a-syngeneic-replicon-cell-transplantation-mouse-model
#10
Sepideh Levander, Fredrik Holmström, Lars Frelin, Gustaf Ahlén, Daniel Rupp, Gang Long, Ralf Bartenschlager, Matti Sällberg
OBJECTIVE: HCV is characterised by its ability to establish chronic infection in hepatocytes and to replicate in the presence of an inflammation. We mimicked this situation in vivo in immune-competent mice by syngeneic transplantation of HCV replicon-containing mouse hepatoma cells. DESIGN: A total of 5 million H-2(b) positive Hep56.1D cells, carrying a subgenomic genotype (gt) 2a replicon (HCV replicon cells) or stably expressing comparable levels of the HCV NS3/4A protease/helicase complex (NS3/4A hepatoma cells), were injected subcutaneously into syngeneic H-2(b)-restricted mice...
June 23, 2017: Gut
https://www.readbyqxmd.com/read/28646017/ror%C3%AE-modulates-semaphorin-3e-transcription-and-neurovascular-interaction-in-pathological-retinal-angiogenesis
#11
Ye Sun, Chi-Hsiu Liu, Zhongxiao Wang, Steven S Meng, Samuel B Burnim, John Paul SanGiovanni, Theodore M Kamenecka, Laura A Solt, Jing Chen
Pathological proliferation of retinal blood vessels commonly causes vision impairment in proliferative retinopathies, including retinopathy of prematurity. Dysregulated crosstalk between the vasculature and retinal neurons is increasingly recognized as a major factor contributing to the pathogenesis of vascular diseases. Class 3 semaphorins (SEMA3s), a group of neuron-secreted axonal and vascular guidance factors, suppress pathological vascular growth in retinopathy. However, the upstream transcriptional regulators that mediate the function of SEMA3s in vascular growth are poorly understood...
June 23, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28645309/herpes-simplex-virus-1-infects-the-olfactory-bulb-shortly-following-ocular-infection-and-exhibits-a-long-term-inflammatory-profile-in-the-form-of-effector-and-hsv-1-specific-t-cells
#12
Chandra M Menendez, Daniel J J Carr
BACKGROUND: Herpes simplex virus 1 (HSV-1) infection can result in a life-threatening condition known as herpes simplex encephalitis (HSE). Trafficking patterns by which the virus reaches the central nervous system (CNS) following ocular infection are unresolved. We evaluated early viral dissemination pathways following ocular infection that involve trafficking to the olfactory bulb (OB). Additionally, we have characterized the capacity of HSV-1 to establish latency within OB tissue and profiled the local T lymphocyte response over the course of the acute infection into latency...
June 23, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28644966/an-immunosuppressive-function-of-interleukin-35-in-chronic-hepatitis-c-virus-infection
#13
Siqi Liu, Qian Zhang, Xue Shao, Wenrui Wang, Chuanhui Zhang, Zhenjing Jin
Interleukin (IL)-35, a newly identified member of the IL-12 cytokine family, has been reported to suppress inflammation and induce immunotolerance. However, little is known regarding the role of IL-35 during chronic hepatitis C virus (HCV) infection. Herein, we measured the serum IL-35 concentration of 73 patients with hepatitis C and 22 healthy individuals, as well as further investigated the modulatory function of IL-35 on CD4(+)CD25(+)CD127(dim/-) regulatory T cells (Tregs) and on hepatocytes infected with HCV in cell culture (HCVcc)...
June 20, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28643847/ncr1-deficiency-diminishes-the-generation-of-protective-murine-cytomegalovirus-antibodies-by-limiting-follicular-helper-t-cell-maturation
#14
Antonija Miletic, Maja Lenartic, Branka Popovic, Ilija Brizic, Tihana Trsan, Karmela Miklic, Ofer Mandelboim, Astrid Krmpotic, Stipan Jonjic
NKp46/NCR1 is an activating NK-cell receptor implicated in the control of various viral and bacterial infections. Recent findings also suggest that it plays a role in shaping the adaptive immune response to pathogens. Using NCR1-deficient (NCR1(gfp/gfp) ) mice we provide evidence for the role of NCR1 in antibody response to mouse cytomegalovirus infection (MCMV). The absence of NCR1 resulted in impaired maturation, function and NK-cell migration to regional lymph nodes. In addition, CD4(+) T-cell activation and follicular helper T-cell (Tfh) generation were reduced, leading to inferior germinal center (GC) B-cell maturation...
June 23, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28642758/time-and-antigen-stimulation-history-influence-memory-cd8-t-cell-bystander-responses
#15
Matthew D Martin, Qiang Shan, Hai-Hui Xue, Vladimir P Badovinac
Memory CD8 T cells can be activated and induced to produce cytokines and increase stores of cytolytic proteins not only in response to cognate antigen (Ag) but also in response to inflammatory cytokines (bystander responses). Importantly, bystander memory CD8 T cell functions have been shown to be dependent upon memory CD8 T cell fitness, since exhausted CD8 T cells have diminished capacity to respond to inflammatory cues. While it is known that memory CD8 T cell functional abilities, including ability to produce cytokines in response to cognate Ag, change with time after initial Ag encounter and upon multiple Ag stimulations (e...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28642743/hiv-1-nef-signaling-in-intestinal-mucosa-epithelium-suggests-the-existence-of-an-active-inter-kingdom-crosstalk-mediated-by-exosomes
#16
REVIEW
Cristina Felli, Olimpia Vincentini, Marco Silano, Andrea Masotti
The human intestinal mucosal surface represents the first defense against pathogens and regulates the immune response through the combination of epithelial cell (EC) functions and immunological factors. ECs act as sensors of luminal stimuli and interact with the immune cells through signal-transduction pathways, thus representing the first barrier that HIV-1 virus encounters during infection. In particular, the HIV-1 Nef protein plays a crucial role in viral invasion and replication. Nef is expressed early during viral infection and interacts with numerous cellular proteins as a scaffold/adaptor...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28641561/induction-of-humoral-and-cellular-immune-responses-in-mice-by-multiepitope-vaccines-composing-of-both-t-and-b-lymphocyte-epitopes-of-mage-a3which-are-recombined-into-hbcag
#17
Qingxin Chen, Wenshu Li, Pengfei Wang, Huanyi Shao, Yujie Ding, Wenhuan Wang, Danwei Cen, Yiqi Cai, Xiangyang Xue, Lifang Zhang, Guanbao Zhu
MAGE-A3 is highly expressed in many kinds of malignant diseases, and considered to be an ideal candidate for anti-tumor vaccine. To improve the immunogenicity of epitopes of MAGE-A3, hepatitis B virus core antigen (HBcAg) was used as an immune-carrier by insertion epitopes at HBcAg major immunodominant region (HBcAg(MIR)). In present study, we designed three kinds of MAGE-A3 multiepitopes containing T and B-cell dominant epitope-rich peptides, and constructed three recombinant chimeras of HBcAg(MIR)/MAGE-A3(EPI-1), HBcAg(MIR)/MAGE-A3(EPI-2), and HBcAg(MIR)/MAGE-A3(EPI-3) with prokaryotic codon optimization...
June 20, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28641539/role-of-host-factors-on-the-regulation-of-tat-mediated-hiv-1-transcription
#18
Guillaume Mousseau, Susana T Valente
BACKGROUND: The viral transactivator Tat protein is a key modulator of HIV-1 replication, as it regulates transcriptional elongation from the integrated proviral genome. Tat recruits the human transcription elongation factor b, and other host proteins, such as the super elongation complex, to activate the cellular RNA polymerase II, normally stalled shortly after transcription initiation at the HIV promoter. By means of a complex set of interactions with host cellular factors, Tat determines the fate of viral activity within the infected cell...
June 22, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28641535/hiv-1-transcription-inhibitors-increase-the-synthesis-of-viral-non-coding-rna-that-contribute-to-latency
#19
Yao A Akpamagbo, Catherine DeMarino, Michelle L Pleet, Angela Schwab, Myosotys Rodriguez, Robert A Barclay, Gavin Sampey, Sergey Iordanskiy, Nazira El-Hage, Fatah Kashanchi
BACKGROUND: HIV-1 can be preserved in long-lived resting CD4+ T- and myeloid cells, forming a viral reservoir in tissues of the infected individuals. Infected patients primarily receive cART, which, to date, is the most efficient treatment against HIV/AIDS. However, the major problem in the eradication of HIV-1 from patients is the lack of therapeutic approaches to recognize the latent HIV-1 provirus and to eliminate latently infected cells. RESULTS: In the current review, we describe the effect of HIV-1 transcriptional inhibitors CR8#13 and F07#13 using a series of in vitro and in vivo assays...
June 22, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28639194/rnaa-induced-by-tata-box-targeting-micrornas
#20
Yijun Zhang, Hui Zhang
Recent studies reveal that some nuclear microRNAs (miRNA) and synthesized siRNAs target gene promoters to activate gene transcription (RNAa). Interestingly, our group identified a novel HIV-1-encoded miRNA, miR-H3, which targets specifically the core promoter TATA box of HIV-1 and activates viral gene expression. Depletion of miR-H3 significantly impaired the replication of HIV-1. miR-H3 mimics could activate viruses from CD4(+) T cells isolated from patients receiving suppressive highly active antiretroviral therapy, which is very intriguing for reducing HIV-1 latent reservoir...
2017: Advances in Experimental Medicine and Biology
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