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https://www.readbyqxmd.com/read/28634571/current-immunotherapeutic-strategies-to-enhance-oncolytic-virotherapy
#1
REVIEW
Daniel E Meyers, Amanda A Wang, Chandini M Thirukkumaran, Don G Morris
Oncolytic viruses (OV) represent a promising strategy to augment the spectrum of cancer therapeutics. For efficacy, they rely on two general mechanisms: tumor-specific infection/cell-killing, followed by subsequent activation of the host's adaptive immune response. Numerous OV genera have been utilized in clinical trials, ultimately culminating in the 2015 Food and Drug Administration approval of a genetically engineered herpes virus, Talminogene laherparepvec (T-VEC). It is generally accepted that OV as monotherapy have only modest clinical efficacy...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28634034/absence-of-%C3%AE-chain-in-keratinocytes-alters-chemokine-secretion-resulting-in-reduced-immune-cell-recruitment
#2
Karolin Nowak, Daniela Linzner, Adrian J Thrasher, Paul F Lambert, Wei Li Di, Siobhan O Burns
Loss of function mutations in the common gamma (γc) chain cytokine receptor subunit give rise to severe combined immunodeficiency (SCID) characterised by lack of T and natural killer cells and infant death from infection. Haematopoietic stem cell transplantation or gene therapy offer cure but despite successful replacement of lymphoid immune lineages a long-term risk of severe cutaneous human papilloma virus (HPV) infections persists, possibly related to persistent γc-deficiency in other cell types. Here we demonstrate that keratinocytes, the only cell type directly infected by HPV, express functional γc and its co-receptors...
June 17, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28630341/pig-model-mimicking-chronic-hepatitis-e-virus-infection-in-immunocompromised-patients-to-assess-immune-correlates-during-chronicity
#3
Dianjun Cao, Qian M Cao, Sakthivel Subramaniam, Danielle M Yugo, C Lynn Heffron, Adam J Rogers, Scott P Kenney, Debin Tian, Shannon R Matzinger, Christopher Overend, Nicholas Catanzaro, Tanya LeRoith, Heng Wang, Pablo Piñeyro, Nicole Lindstrom, Sherrie Clark-Deener, Lijuan Yuan, Xiang-Jin Meng
Chronic hepatitis E virus (HEV) infection is a significant clinical problem in immunocompromised individuals such as organ transplant recipients, although the mechanism remains unknown because of the lack of an animal model. We successfully developed a pig model of chronic HEV infection and examined immune correlates leading to chronicity. The conditions of immunocompromised patients were mimicked by treating pigs with an immunosuppressive regimen including cyclosporine, azathioprine, and prednisolone. Immunocompromised pigs infected with HEV progressed to chronicity, because 8/10 drug-treated HEV-infected pigs continued fecal virus shedding beyond the acute phase of infection, whereas the majority (7/10) of mock-treated HEV-infected pigs cleared fecal viral shedding at 8 wk postinfection...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28630092/characterization-of-high-avidity-cytomegalovirus-specific-t-cells-with-differential-tetramer-binding-coappearing-after-allogeneic-stem-cell-transplantation
#4
Justyna Ogonek, Kriti Verma, Christian Schultze-Florey, Pavankumar Varanasi, Susanne Luther, Patrick Schweier, Wolfgang Kühnau, Gudrun Göhring, Elke Dammann, Michael Stadler, Arnold Ganser, Ulrike Koehl, Christian Koenecke, Eva M Weissinger, Lothar Hambach
CMV reactivation is a major complication after allogeneic stem cell transplantation (SCT). Immune reconstitution of CMV-specific CTLs (CMV-CTLs) is essential for virus control. During CMV-CTL monitoring using mutated HLA/CMV tetramers selectively detecting high-avidity T cells, we observed coappearance of CMV-CTLs with low (CMV tet(low) CTLs) and high tetramer binding (CMV tet(high) CTLs) in 53/115 CMV IgG(+) patients stem cell transplanted from CMV IgG(+) donors. However, the relevance of these coappearing differentially tetramer binding ("dual") CMV-CTLs was unclear...
June 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28628616/therapeutic-administration-of-a-recombinant-human-monoclonal-antibody-reduces-the-severity-of-chikungunya-virus-disease-in-rhesus-macaques
#5
Rebecca Broeckel, Julie M Fox, Nicole Haese, Craig N Kreklywich, Soila Sukulpovi-Petty, Alfred Legasse, Patricia P Smith, Michael Denton, Carsten Corvey, Shiv Krishnan, Lois M A Colgin, Rebecca M Ducore, Anne D Lewis, Michael K Axthelm, Marie Mandron, Pierre Cortez, Jonathan Rothblatt, Ercole Rao, Ingo Focken, Kara Carter, Gopal Sapparapau, James E Crowe, Michael S Diamond, Daniel N Streblow
Chikungunya virus (CHIKV) is a mosquito-borne virus that causes a febrile syndrome in humans associated with acute and chronic debilitating joint and muscle pain. Currently no licensed vaccines or therapeutics are available to prevent or treat CHIKV infections. We recently isolated a panel of potently neutralizing human monoclonal antibodies (mAbs), one (4N12) of which exhibited prophylactic and post-exposure therapeutic activity against CHIKV in immunocompromised mice. Here, we describe the development of an engineered CHIKV mAb, designated SVIR001, that has similar antigen binding and neutralization profiles to its parent, 4N12...
June 19, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28628043/immunotherapy-for-transplantation-associated-viral-infections
#6
Claire Roddie, Karl S Peggs
Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections following allogeneic hematopoietic stem cell transplantation (HSCT) are a major cause of morbidity and mortality. Early clinical trials demonstrate that adoptive transfer of donor-derived virus-specific T cells to restore virus-specific immunity is an effective strategy to control CMV and EBV infection after HSCT, conferring protection in 70%-90% of patients. The field has evolved rapidly to develop solutions to some of the manufacturing challenges identified in early clinical studies, such as prolonged in vitro culture, optimization of the purity of the virus-specific T cell product, the potential limitations of targeting a single viral antigen, and how to manage the patient with a virus-naive donor...
June 19, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28627820/performance-of-the-liaison%C3%A2-xl-murex-rechtlv-i-ii-immunoassay-in-the-detection-of-htlv-1-2-antibodies-in-serum
#7
Pierre Gantner, Aurelie Velay, Nicolas Guigue, Heidi Barth, Marie-Josee Wendling, Constance Delaugerre, Samira Fafi-Kremer
BACKGROUND: Human T-cell lymphotropic virus type 1 and 2 (HTLV-1/2) immunoassays are used for blood screen- ing from blood products, milk, and organ donors. METHODS: We assessed the performance of the DiaSorin Liaison® XL murex recHTLV-I/II immunoassay relative to the Abbott Architect® rHTLV-I/II immunoassay and with the Innogenetics immunoblot as confirmation. RESULTS: A panel of HTLV positive (n = 66) and negative (n = 30) sera was tested in both techniques within the same freeze/thaw cycle...
May 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28624961/phenotypic-and-functional-characterization-of-t-cells-in-white-matter-lesions-of-multiple-sclerosis-patients
#8
Gijsbert P van Nierop, Marvin M van Luijn, Samira S Michels, Marie-Jose Melief, Malou Janssen, Anton W Langerak, Werner J D Ouwendijk, Rogier Q Hintzen, Georges M G M Verjans
T cells are considered pivotal in the pathology of multiple sclerosis (MS), but their function and antigen specificity are unknown. To unravel the role of T cells in MS pathology, we performed a comprehensive analysis on T cells recovered from paired blood, cerebrospinal fluid (CSF), normal-appearing white matter (NAWM) and white matter lesions (WML) from 27 MS patients with advanced disease shortly after death. The differentiation status of T cells in these compartments was determined by ex vivo flow cytometry and immunohistochemistry...
June 17, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28624237/identification-of-syntaxin-4-as-an-essential-factor-for-the-hepatitis-c-virus-life-cycle
#9
Huimei Ren, Fabian Elgner, Kiyoshi Himmelsbach, Sami Akhras, Bingfu Jiang, Regina Medvedev, Daniela Ploen, Eberhard Hildt
Although there is evidence that multivesicular bodies (MVBs) are involved in the release of hepatitis C virus (HCV), many aspects of HCV release are still not fully understood. The amount of α-taxilin that prevents SNARE (soluble N-ethylmaleimidesensitive factor attachment protein receptor) complex formation by binding to free syntaxin 4 is reduced in HCV-positive cells. Therefore, it was analyzed whether the t-SNARE protein syntaxin 4 which mediates vesicles fusion is involved in the HCV life cycle. HCV-positive cells possess an increased amount of syntaxin 4 protein, although the amount of syntaxin 4-specific transcripts is decreased in HCV-positive Huh7...
June 10, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28622976/differential-binding-of-the-hiv-1-envelope-to-phosphatidylserine-receptors
#10
Linlin Gu, Brian Sims, Alexandre Krendelchtchikov, Edlue Tabengwa, Qiana L Matthews
Prior work has shown that the HIV-1 envelope of the human immunodeficiency virus (HIV) interact directly with T-cell immunoglobulin mucin (TIM) family proteins. Herein, we demonstrate that HIV-1 envelope glycoproteins from varying HIV-1 clades bind differentially to TIM proteins and functionally similar proteins acting as phosphatidylserine (PtdSer) receptors. Using enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR) technology, we show that lysate containing HIV-1 envelope and recombinant HIV-1 envelope glycoproteins bind TIM-4 and advanced glycosylation end product-specific receptor (AGER)...
June 13, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28620645/alloimmunity-but-not-viral-immunity-promotes-allograft-loss-in-a-mouse-model-of-polyomavirus-associated-allograft-injury
#11
Steven C Kim, Jun Wang, Ying Dong, David V Mathews, Joshua A Albrecht, Cynthia P Breeden, Alton B Farris, Aron E Lukacher, Mandy L Ford, Kenneth A Newell, Andrew B Adams
BACKGROUND: The interplay between viral infection and alloimmunity is known to influence the fate of transplanted organs. Clarifying how local virus-associated inflammation/injury and antiviral immunity can alter host alloimmune responses in transplantation remains a critical question. METHODS: We used a mouse model of polyomavirus (PyV) infection and kidney transplantation to investigate the roles of direct viral pathology, the antiviral immune response, and alloimmunity in the pathogenesis of PyV-associated allograft injury...
June 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28619138/newcastle-disease-virus-like-particles-induce-dc-maturation-through-tlr4-nf-%C3%AE%C2%BAb-pathway-and-facilitate-dc-migration-by-ccr7-ccl19-ccl21-axis
#12
Jing Qian, Xiaohong Xu, Jiaxin Ding, Renfu Yin, Yixue Sun, Cong Xue, Jianzhong Wang, Chan Ding, Shengqing Yu, Xiufan Liu, Shunlin Hu, Chunfeng Wang, Yanlong Cong, Zhuang Ding
Newcastle disease virus-like particles (NDV VLPs) are a potential candidate vaccine, as shown by eliciting specific immune response against NDV in mice and chickens. Activation of dendritic cells (DCs) is critical to initiate immune response. However, the mechanism of how NDV VLPs induce DC maturation and migration remains elusive. In this study, we found that NDV VLPs are efficient in DC activation by up-regulating surface MHC II and costimulatory molecules, and proinflammatory cytokines through the TLR4/NF-κB pathway...
May 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28617868/three-mutations-switch-h7n9-influenza-to-human-type-receptor-specificity
#13
Robert P de Vries, Wenjie Peng, Oliver C Grant, Andrew J Thompson, Xueyong Zhu, Kim M Bouwman, Alba T Torrents de la Pena, Marielle J van Breemen, Iresha N Ambepitiya Wickramasinghe, Cornelis A M de Haan, Wenli Yu, Ryan McBride, Rogier W Sanders, Robert J Woods, Monique H Verheije, Ian A Wilson, James C Paulson
The avian H7N9 influenza outbreak in 2013 resulted from an unprecedented incidence of influenza transmission to humans from infected poultry. The majority of human H7N9 isolates contained a hemagglutinin (HA) mutation (Q226L) that has previously been associated with a switch in receptor specificity from avian-type (NeuAcα2-3Gal) to human-type (NeuAcα2-6Gal), as documented for the avian progenitors of the 1957 (H2N2) and 1968 (H3N2) human influenza pandemic viruses. While this raised concern that the H7N9 virus was adapting to humans, the mutation was not sufficient to switch the receptor specificity of H7N9, and has not resulted in sustained transmission in humans...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28615708/epitope-mapping-and-kinetics-of-cd4-t-cell-immunity-to-pneumonia-virus-of-mice-in-the-c57bl-6-strain
#14
Lana Vandersarren, Cedric Bosteels, Manon Vanheerswynghels, James J Moon, Andrew J Easton, Gert Van Isterdael, Sophie Janssens, Bart N Lambrecht, Mary J van Helden
Pneumonia virus of mice (PVM) infection has been widely used as a rodent model to study the closely related human respiratory syncytial virus (hRSV). While T cells are indispensable for viral clearance, they also contribute to immunopathology. To gain more insight into mechanistic details, novel tools are needed that allow to study virus-specific T cells in C57BL/6 mice as the majority of transgenic mice are only available on this background. While PVM-specific CD8 T cell epitopes were recently described, so far no PVM-specific CD4 T cell epitopes have been identified within the C57BL/6 strain...
June 14, 2017: Scientific Reports
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
#15
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/28615208/deficiency-of-the-nod-like-receptor-nlrc5-results-in-decreased-cd8-t-cell-function-and-impaired-viral-clearance
#16
Christopher R Lupfer, Kate L Stokes, Teneema Kuriakose, Thirumala-Devi Kanneganti
Pathogen recognition receptors are vital components of the immune system. Engagement of these receptors is important not only for instigation of innate immune responses to invading pathogens but also for initiating the adaptive immune response. Members of the NOD-like receptor (NLR) family of pathogen recognition receptors have important roles in orchestrating this response. The NLR family member, NLRC5 regulates major histocompatibility complex class I (MHC-I) expression during various types of infections, but its role in immunity to influenza A virus (IAV) is not well studied...
June 14, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28614791/human-vaccination-against-plasmodium-vivax-duffy-binding-protein-induces-strain-transcending-antibodies
#17
Ruth O Payne, Sarah E Silk, Sean C Elias, Kathryn H Milne, Thomas A Rawlinson, David Llewellyn, A Rushdi Shakri, Jing Jin, Geneviève M Labbé, Nick J Edwards, Ian D Poulton, Rachel Roberts, Ryan Farid, Thomas Jørgensen, Daniel Gw Alanine, Simone C de Cassan, Matthew K Higgins, Thomas D Otto, James S McCarthy, Willem A de Jongh, Alfredo Nicosia, Sarah Moyle, Adrian Vs Hill, Eleanor Berrie, Chetan E Chitnis, Alison M Lawrie, Simon J Draper
BACKGROUND: Plasmodium vivax is the most widespread human malaria geographically; however, no effective vaccine exists. Red blood cell invasion by the P. vivax merozoite depends on an interaction between the Duffy antigen receptor for chemokines (DARC) and region II of the parasite's Duffy-binding protein (PvDBP_RII). Naturally acquired binding-inhibitory antibodies against this interaction associate with clinical immunity, but it is unknown whether these responses can be induced by human vaccination...
June 15, 2017: JCI Insight
https://www.readbyqxmd.com/read/28613916/human-cd8-t-cells-damage-non-infected-epithelial-cells-during-influenza-virus-infection-in-vitro
#18
Carolien E van de Sandt, Montserrat Bárcena, Abraham J Koster, Jennifer Kasper, Charles J Kirkpatrick, Dana P Scott, Rory D de Vries, Susanne Herold, Guus F Rimmelzwaan, Thijs Kuiken, Kirsty R Short
During severe influenza A virus (IAV) infections a large amount of damage to the pulmonary epithelium is the result of the anti-viral immune response. Specifically, whilst CD8+ T cells are important for killing IAV-infected cells, during a severe IAV infection they can damage uninfected epithelial cells. At present, the mechanisms by which this occurs are unclear. Here, we used a novel in vitro co-culture model of human NCl-H441 cells and CD8+ T cells in order to provide a new insight into how CD8+ T cells may affect uninfected epithelial cells during severe IAV infections...
June 14, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28612840/toll-like-receptor-3-in-nasal-cd103-dendritic-cells-is-involved-in-immunoglobulin-a-production
#19
H Takaki, S Kure, H Oshiumi, Y Sakoda, T Suzuki, A Ainai, H Hasegawa, M Matsumoto, T Seya
Intranasal inoculation with influenza hemagglutinin subunit with polyinosine-polycytidylic (polyI:C), a synthetic analog for double-stranded RNA, enhances production of vaccine-specific immunoglobulin (Ig) A, which is superior to IgG in prophylactic immunity. The mechanism whereby polyI:C skews to IgA production in the nasal-associated lymph tissue (NALT) was investigated in mouse models. Nasally instilled polyI:C was endocytosed into CD103(+) dendritic cells (DCs) and induced T-cell activation, including interferon (IFN)-γ production...
June 14, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28612032/genetics-and-molecular-biology-of-epstein-barr-virus-encoded-bart-microrna-a-paradigm-for-viral-modulation-of-host-immune-response-genes-and-genome-stability
#20
REVIEW
David H Dreyfus
Epstein-Barr virus, a ubiquitous human herpesvirus, is associated through epidemiologic evidence with common autoimmune syndromes and cancers. However, specific genetic mechanisms of pathogenesis have been difficult to identify. In this review, the author summarizes evidence that recently discovered noncoding RNAs termed microRNA encoded by Epstein-Barr virus BARF (BamHI A right frame) termed BART (BamHI A right transcripts) are modulators of human immune response genes and genome stability in infected and bystander cells...
2017: Journal of Immunology Research
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