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Virus-specific T cell

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https://www.readbyqxmd.com/read/28530712/the-microrna-mir-31-inhibits-cd8-t-cell-function-in-chronic-viral-infection
#1
Howell F Moffett, Adam N R Cartwright, Hye-Jung Kim, Jernej Godec, Jason Pyrdol, Tarmo Äijö, Gustavo J Martinez, Anjana Rao, Jun Lu, Todd R Golub, Harvey Cantor, Arlene H Sharpe, Carl D Novina, Kai W Wucherpfennig
During infection, antigen-specific T cells undergo tightly regulated developmental transitions controlled by transcriptional and post-transcriptional regulation of gene expression. We found that the microRNA miR-31 was strongly induced by activation of the T cell antigen receptor (TCR) in a pathway involving calcium and activation of the transcription factor NFAT. During chronic infection with lymphocytic choriomeningitis virus (LCMV) clone 13, miR-31-deficent mice recovered from clinical disease, while wild-type mice continued to show signs of disease...
May 22, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28530508/influence-of-transmitted-virus-on-the-host-s-immune-response-a-case-study
#2
Shahzma Merani, Michaela Lucas, Pooja Deshpande, Katja Pfafferott, Abha Chopra, Don Cooper, Shay Leary, Fabio Luciani, Silvana Gaudieri
Host hepatitis C virus (HCV)-specific T cell responses and the ability of the virus to escape this response are important correlates of infection outcome. Understanding this host-viral interplay has been difficult given the often asymptomatic nature of acute HCV infection. We studied a recent transmission case to determine whether adapted viral strains can be transmitted and influence the recipient's anti-HCV T cell response. The diversity of viral populations was examined using next-generation sequencing, and HCV-specific T cell interferon (IFN)-γ responses were assessed using a peptide panel representing the autologous viruses...
May 22, 2017: Viral Immunology
https://www.readbyqxmd.com/read/28529974/a-glycosylphosphatidylinositol-anchored-carbonic-anhydrase-related-protein-of-toxoplasma-gondii-is-important-for-rhoptry-biogenesis-and-virulence
#3
Nathan M Chasen, Beejan Asady, Leandro Lemgruber, Rossiane C Vommaro, Jessica C Kissinger, Isabelle Coppens, Silvia N J Moreno
Carbonic anhydrase-related proteins (CARPs) have previously been described as catalytically inactive proteins closely related to α-carbonic anhydrases (α-CAs). These CARPs are found in animals (both vertebrates and invertebrates) and viruses as either independent proteins or domains of other proteins. We report here the identification of a new CARP (TgCA_RP) in the unicellular organism Toxoplasma gondii that is related to the recently described η-class CA found in Plasmodium falciparum. TgCA_RP is posttranslationally modified at its C terminus with a glycosylphosphatidylinositol anchor that is important for its localization in intracellular tachyzoites...
May 2017: MSphere
https://www.readbyqxmd.com/read/28529001/a-single-intranasal-administration-of-virus-like-particle-vaccine-induces-an-efficient-protection-for-mice-against-human-respiratory-syncytial-virus
#4
Yue-Ying Jiao, Yuan-Hui Fu, Yi-Fei Yan, Ying Hua, Yao Ma, Xiu-Juan Zhang, Jing-Dong Song, Xiang-Lei Peng, Jiaqiang Huang, Tao Hong, Jin-Sheng He
Human respiratory syncytial virus (RSV) is an important pediatric pathogen causing acute viral respiratory disease in infants and young children. However, no licensed vaccines are currently available. Virus-like particles (VLPs) may bring new hope to producing RSV VLP vaccine with high immunogenicity and safety. Here, we constructed the recombinants of matrix protein (M) and fusion glycoprotein (F) of RSV, respectively into a replication-deficient first-generation adenoviral vector (FGAd), which were used to co-infect Vero cells to assemble RSV VLPs successfully...
May 18, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28527722/crispr-cas9-mediated-ccr5-ablation-in-human-hematopoietic-stem-progenitor-cells-confers-hiv-1-resistance-in%C3%A2-vivo
#5
Lei Xu, Huan Yang, Yang Gao, Zeyu Chen, Liangfu Xie, Yulin Liu, Ying Liu, Xiaobao Wang, Hanwei Li, Weifeng Lai, Yuan He, Anzhi Yao, Liying Ma, Yiming Shao, Bin Zhang, Chengyan Wang, Hu Chen, Hongkui Deng
Transplantation of hematopoietic stem cells (HSCs) with a naturally occurring CCR5 mutation confers a loss of detectable HIV-1 in the patient, making ablation of the CCR5 gene in HSCs an ideal therapy for an HIV-1 cure. Although CCR5 disruption has been attempted in CD4(+) T cells and hematopoietic stem/progenitor cells (HSPCs), efficient gene editing with high specificity and long-term therapeutic potential remains a major challenge for clinical translation. Here, we established a CRISPR/Cas9 gene editing system in human CD34(+) HSPCs and achieved efficient CCR5 ablation evaluated in long-term reconstituted NOD/Prkdc(scid)/IL-2Rγ(null) mice...
May 17, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28526760/tissue-resident-t-cells-in-hepatitis-b-a-new-target-for-cure
#6
Fabian J Bolte, Barbara Rehermann
A hallmark of chronic hepatitis B virus (HBV) infection is the functional impairment and depletion of antiviral T cells. In this issue of JEM, Pallett et al. (https://doi.org/10.1084/jem.20162115) identify a reservoir of functional HBV-specific T cells among liver-resident T cells.
May 19, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28523920/expression-of-bovine-rotavirus-vp8-and-preparation-of-igy-antibodies-against-recombinant-vp8
#7
H S Kim, B Lee, S Y Han, Y T Jung
Group A rotavirus is the leading cause of acute gastroenteritis in cattle and swine. Although, vaccination against this virus is an effective strategy for prevention, additional strategy to control disease is necessary. Egg yolk immunoglobulin (IgY)-based passive immunization could be a better option in preventing this disease. Bovine rotavirus (BRV) is group A rotavirus and possesses a genome of 11 segments of double-stranded RNA. The outer layer of capsid is composed of two proteins (VP7 and VP4), which induce virus neutralizing antibodies...
2017: Acta Virologica
https://www.readbyqxmd.com/read/28522585/herpes-simplex-virus-glycoprotein-d-targets-a-specific-dendritic-cell-subset-and-improves-the-performance-of-vaccines-to-human-papillomavirus-associated-tumors
#8
Bruna F M M Porchia, Ana Carolina R Moreno, Rodrigo N Ramos, Mariana O Diniz, Laís Helena T M de Andrade, Daniela S Rosa, José Alexandre M Barbuto, Silvia B Boscardin, Luís Carlos S Ferreira
Cervical cancer is a major public health problem and one of the leading causes of cancer deaths in women. Virtually all cases of cervical cancer, as well as a growing share of anal and head/neck tumors, are associated with human papillomavirus (HPV) infection. Despite the effectiveness, the available prophylactic vaccines do not benefit women with cervical lesions or cancer. Therefore, the search of new immunotherapeutic approaches to treat HPV-induced tumors is still a priority. The present study characterizes a therapeutic antitumor vaccine based on the genetic fusion of the Herpes simplex virus-1 (HSV-1) glycoprotein D (gD) with the E7 oncoprotein from HPV-16 (gDE7)...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28520963/humoral-and-innate-antiviral-immunity-as-tools-to-clear-persistent-hiv-infection
#9
Guido Ferrari, Justin Pollara, Georgia D Tomaras, Barton F Haynes
Human immunodeficiency virus (HIV) type 1 uses the CD4 molecule as its principal receptor to infect T cells. HIV-1 integrates its viral genome into the host cell, leading to persistent infection wherein HIV-1 can remain transcriptionally silent in latently infected CD4+ T cells. On reactivation of replication-competent provirus, HIV-1 envelope glycoproteins (Env) are expressed and accumulate on the cell surface, allowing infected cells to be detected and targeted by endogenous immune responses or immune interventions...
March 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28514685/virus-like-particles-identify-an-hiv-v1v2-apex-binding-neutralizing-antibody-that-lacks-a-protruding-loop
#10
Evan M Cale, Jason Gorman, Nathan A Radakovich, Ema T Crooks, Keiko Osawa, Tommy Tong, Jiaqi Li, Raju Nagarajan, Gabriel Ozorowski, David R Ambrozak, Mangai Asokan, Robert T Bailer, Anthony K Bennici, Xuejun Chen, Nicole A Doria-Rose, Aliaksandr Druz, Yu Feng, M Gordon Joyce, Mark K Louder, Sijy O'Dell, Courtney Oliver, Marie Pancera, Mark Connors, Thomas J Hope, Thomas B Kepler, Richard T Wyatt, Andrew B Ward, Ivelin S Georgiev, Peter D Kwong, John R Mascola, James M Binley
Most HIV-1-specific neutralizing antibodies isolated to date exhibit unusual characteristics that complicate their elicitation. Neutralizing antibodies that target the V1V2 apex of the HIV-1 envelope (Env) trimer feature unusually long protruding loops, which enable them to penetrate the HIV-1 glycan shield. As antibodies with loops of requisite length are created through uncommon recombination events, an alternative mode of apex binding has been sought. Here, we isolated a lineage of Env apex-directed neutralizing antibodies, N90-VRC38...
May 16, 2017: Immunity
https://www.readbyqxmd.com/read/28510446/modularly-constructed-synthetic-granzyme-b-molecule-enables-interrogation-of-intracellular-proteases-for-targeted-cytotoxicity
#11
Patrick Ho, Christopher Ede, Yvonne Y Chen
Targeted therapies promise to increase the safety and efficacy of treatments against diseases ranging from cancer to viral infections. However, the vast majority of targeted therapeutics relies on the recognition of extracellular biomarkers, which are rarely restricted to diseased cells and are thus prone to severe and sometimes-fatal off-target toxicities. In contrast, intracellular antigens present a diverse yet underutilized repertoire of disease markers. Here, we report a protein-based therapeutic platform-termed Cytoplasmic Oncoprotein VErifier and Response Trigger (COVERT)-which enables the interrogation of intracellular proteases to trigger targeted cytotoxicity...
May 22, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28507788/adaptive-t-cell-responses-induced-by-oncolytic-herpes-simplex-virus-granulocyte-macrophage-colony-stimulating-factor-therapy-expanded-by-dendritic-cell-and-cytokine-induced-killer-cell-adoptive-therapy
#12
Jun Ren, William R Gwin, Xinna Zhou, Xiaoli Wang, Hongyan Huang, Ni Jiang, Lei Zhou, Pankaj Agarwal, Amy Hobeika, Erika Crosby, Zachary C Hartman, Michael A Morse, Kevin H Eng, H Kim Lyerly
Purpose: Although local oncolytic viral therapy (OVT) may enhance tumor lysis, antigen release, and adaptive immune responses, systemic antitumor responses post-therapy are limited. Adoptive immunotherapy with autologous dendritic cells (DC) and cytokine-induced killer cells (DC-CIK) synergizes with systemic therapies. We hypothesized that OVT with Herpes Simplex Virus-granulocyte macrophage-colony-stimulating factor (HSV-GM-CSF) would induce adaptive T cell responses that could be expanded systemically with sequential DC-CIK therapy...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28505602/unusual-antigen-presentation-offers-new-insight-into-hiv-vaccine-design
#13
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...
May 12, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28502901/neuraminidase-activity-of-blue-eye-disease-porcine-rubulavirus-specificity-affinity-and-inhibition-studies
#14
Gerardo Santos-López, María T Borraz-Argüello, Luis Márquez-Domínguez, Juan Carlos Flores-Alonso, Humberto Ramírez-Mendoza, Bernard Priem, Sébastien Fort, Verónica Vallejo-Ruiz, Julio Reyes-Leyva, Irma Herrera-Camacho
Porcine rubulavirus (PorPV), also known as La Piedad Michoacan Virus (LPMV) causes encephalitis and reproductive failure in newborn and adult pigs, respectively. The hemagglutinin-neuraminidase (HN) glycoprotein is the most exposed and antigenic of the virus proteins. HN plays central roles in PorPV infection; i.e., it recognizes sialic acid-containing cell receptors that mediate virus attachment and penetration; in addition, its neuraminidase (sialic acid releasing) activity has been proposed as a virulence factor...
May 6, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28500340/both-haemagglutinin-specific-antibody-and-t-cell-responses-induced-by-a-chimpanzee-adenoviral-vaccine-confer-protection-against-influenza-h7n9-viral-challenge
#15
Xiang Wang, Weihui Fu, Songhua Yuan, Xi Yang, Yufeng Song, Lulu Liu, Yudan Chi, Tao Cheng, Man Xing, Yan Zhang, Chao Zhang, Yong Yang, Caihong Zhu, Xiaoyan Zhang, Sidong Xiong, Jianqing Xu, Dongming Zhou
Since 2013, the outbreak or sporadic infection of a new reassortant H7N9 influenza virus in China has resulted in hundreds of deaths and thousands of illnesses. An H7N9 vaccine is urgently needed, as a licensed human vaccine against H7N9 influenza is currently not available. Here, we developed a recombinant adenovirus-based vaccine, AdC68-H7HA, by cloning the H7N9 haemagglutinin (HA) gene into the chimpanzee adenoviral vector AdC68. The efficacy of AdC68-H7HA was evaluated in mice as well as guinea pigs. For comparison, an H7N9 DNA vaccine based on HA was also generated and tested in mice and guinea pigs...
May 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28500077/alternative-start-sites-downstream-of-nonsense-mutations-drive-antigen-presentation-and-tolerance-induction-to-c-terminal-epitopes
#16
Scott N Ashley, Suryanarayan Somanathan, Christian Hinderer, Maxwell Arias, Deirdre McMenamin, Christine Draper, James M Wilson
CTL responses to the transgene product remain an active area of concern for the gene therapy field. A patient's underlying genetic mutation may influence the qualitative nature of these potentially destructive T cell responses. Individuals with a mutation that introduces a premature termination codon (PTC) that prevents synthesis of the full-length peptide are considered more likely to mount a transgene-specific T cell response because of a lack of immune tolerance to C-terminal epitopes as a consequence of absent endogenous Ag presentation...
May 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28499553/nasal-delivery-of-protollin-adjuvanted-h5n1-vaccine-induces-enhanced-systemic-as-well-as-mucosal-immunity-in-mice
#17
Weiping Cao, Jin Hyang Kim, Adrian J Reber, Mary Hoelscher, Jessica A Belser, Xiuhua Lu, Jacqueline M Katz, Shivaprakash Gangappa, Martin Plante, David S Burt, Suryaprakash Sambhara
Sporadic, yet frequent human infections with avian H5N1 influenza A viruses continue to pose a potential pandemic threat. Poor immunogenicity of unadjuvanted H5N1 vaccines warrants developing novel adjuvants and formulations as well as alternate delivery systems to improve their immunogenicity and efficacy. Here, we show that Protollin, a nasal adjuvant composed of Neisseria meningitides outer membrane proteins non-covalently linked to Shigella flexneri 2a lipopolysaccharide, is a potent nasal adjuvant for an inactivated split virion H5N1 clade 1 A/Viet Nam1203/2004 (A/VN/1203/04) vaccine in a mouse model...
June 5, 2017: Vaccine
https://www.readbyqxmd.com/read/28497777/phase-i-ii-clinical-trial-to-assess-safety-and-efficacy-of-intratumoral-and-subcutaneous-injection-of-hvj-e-in-castration-resistant-prostate-cancer-patients
#18
K Fujita, Y Nakai, A Kawashima, T Ujike, A Nagahara, T Nakajima, T Inoue, C M Lee, M Uemura, Y Miyagawa, Y Kaneda, N Nonomura
Inactivated Sendai virus particles (hemagglutinating virus of Japan envelope (HVJ-E)) have a novel antitumor effect: HVJ-E fused to prostate cancer cells via cell surface receptor causes apoptosis of prostate cancer cells in vitro and in vivo. HVJ-E also induces antitumor immunity by activating natural killer (NK) cells and cytotoxic T cells and suppressing regulatory T cells in vivo. We conducted an open-label, single-arm, phase I/II clinical trial in patients with castration-resistant prostate cancer (CRPC) to determine the safety and efficacy of intratumoral and subcutaneous injection of HVJ-E...
May 12, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28496337/immunogenicity-of-oncolytic-vaccinia-viruses-jx-gfp-and-tg6002-in-a-human-melanoma-in-vitro-model-studying-immunogenic-cell-death-dendritic-cell-maturation-and-interaction-with-cytotoxic-t-lymphocytes
#19
B Heinrich, J Klein, M Delic, K Goepfert, V Engel, L Geberzahn, M Lusky, P Erbs, X Preville, M Moehler
Oncolytic virotherapy is an emerging immunotherapeutic modality for cancer treatment. Oncolytic viruses with genetic modifications can further enhance the oncolytic effects on tumor cells and stimulate antitumor immunity. The oncolytic vaccinia viruses JX-594-GFP+/hGM-CSF (JX-GFP) and TG6002 are genetically modified by secreting granulocyte-macrophage colony-stimulating factor (GM-CSF) or transforming 5-fluorocytosine (5-FC) into 5-fluorouracil (5-FU). We compared their properties to kill tumor cells and induce an immunogenic type of cell death in a human melanoma cell model using SK29-MEL melanoma cells...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28495463/development-of-an-animal-model-of-progressive-vaccinia-in-nu-nu-mice-and-the-use-of-bioluminescence-imaging-for-assessment-of-the-efficacy-of-monoclonal-antibodies-against-vaccinial-b5-and-l1-proteins
#20
Marina Zaitseva, Antonia Thomas, Clement A Meseda, Charles Y K Cheung, Claudia G Diaz, Yan Xiang, Shane Crotty, Hana Golding
Bioluminescence imaging (BLI) was used to follow dissemination of recombinant vaccinia virus (VACV) expressing luciferase (IHD-J-Luc) in BALB/c nu/nu mice treated post-challenge with monoclonal antibodies (MAbs) against L1 and B5 VACV proteins in a model of Progressive Vaccinia (PV). Areas Under the flux Curve (AUC) were calculated for viral loads in multiple organs in individual mice. Following scarification with 10(5) pfu, IHD-J-Luc VACV undergoes fast replication at the injection site and disseminates rapidly to the inguinal lymph nodes followed by spleen, liver, and axillary lymph nodes within 2-3 days and before primary lesions are visible at the site of scarification...
May 8, 2017: Antiviral Research
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