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https://www.readbyqxmd.com/read/29341118/inhibition-of-the-fgl2-fc%C3%AE-riib-riii-immunosuppressive-pathway-enhances-antiviral-t-cell-and-b-cell-responses-leading-to-clearance-of-lcmv-cl-13
#1
Olga Klingberg, Ramzi Khattar, Kaveh Farrokhi, Dario Ferri, Nataliya Yavorska, Jianhua Zhang, Hassan Sadozai, Oyedele Adeyi, Andrzej Chruscinski, Gary A Levy, Nazia Selzner
Persistent viruses evade immune detection by interfering with virus-specific innate and adaptive antiviral immune responses. Fibrinogen-Like Protein-2 (FGL2) is a potent effector molecule of CD4+ CD25+ FoxP3+ regulatory T cells (Treg) and exerts its immunosuppressive activity following ligation to its cognate receptor, FcγRIIB/RIII. The role of FGL2 in the pathogenesis of chronic viral infection caused by Lymphocytic Choriomeningitis Virus Clone-13 (LCMV cl-13) was assessed in this study. Chronically infected fgl2+/+ mice had increased plasma levels of FGL2, with reduced expression of the maturation markers, CD80, CD86 and MHC-II on macrophages and dendritic cells (DC) and impaired production of neutralizing antibody...
January 17, 2018: Immunology
https://www.readbyqxmd.com/read/29317703/modeling-tumor-immunity-of-mouse-glioblastoma-by-exhausted-cd8-t-cells
#2
Hiroshi Nakashima, Quazim A Alayo, Pablo Penaloza-MacMaster, Gordon J Freeman, Vijay K Kuchroo, David A Reardon, Soledad Fernandez, Michael Caligiuri, E Antonio Chiocca
T cell exhaustion occurs during chronic infection and cancers. Programmed cell death protein-1 (PD-1) is a major inhibitory checkpoint receptor involved in T cell exhaustion. Blocking antibodies (Abs) against PD-1 or its ligand, PD-L1, have been shown to reverse T cell exhaustion during chronic infection and cancers, leading to improved control of persistent antigen. However, modeling tumor-specific T cell responses in mouse has been difficult due to the lack of reagents to detect and phenotype tumor-specific immune responses...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29315553/acute-stimulation-generates-tim-3-expressing-th1-type-cd4-t-cells-that-persist-in-vivo-and-show-enhanced-effector-function
#3
Jacob V Gorman, John D Colgan
Tim-3 is a surface receptor expressed by Th1-type effector CD4 T cells, which are critical for defense against intracellular pathogens and have been implicated in autoimmune disease. Previous studies showed Tim-3 expression makes Th1 cells more susceptible to apoptosis and also marks functionally impaired T cells that arise due to chronic stimulation. However, other studies suggested Tim-3-expressing Th1 cells do not always have these properties. To further define the relationship between Tim-3 and Th1 cell function, we analyzed the characteristics of Th1 cells that expressed Tim-3 in response to brief stimulation in vitro or an acute viral infection in vivo...
January 9, 2018: Immunology
https://www.readbyqxmd.com/read/29301196/sustained-ifn-i-expression-during-established-persistent-viral-infection-a-bad-seed-for-protective-immunity
#4
REVIEW
Xavier Dagenais-Lussier, Hamza Loucif, Armstrong Murira, Xavier Laulhé, Simona Stäger, Alain Lamarre, Julien van Grevenynghe
Type I interferons (IFN-I) are one of the primary immune defenses against viruses. Similar to all other molecular mechanisms that are central to eliciting protective immune responses, IFN-I expression is subject to homeostatic controls that regulate cytokine levels upon clearing the infection. However, in the case of established persistent viral infection, sustained elevation of IFN-I expression bears deleterious effects to the host and is today considered as the major driver of inflammation and immunosuppression...
December 30, 2017: Viruses
https://www.readbyqxmd.com/read/29284207/production-of-transgenic-pigs-using-the-pgfap-creert2-egfploxp-inducible-system-for-central-nervous-system-disease-models
#5
Seon-Ung Hwang, Kiyoung Eun, Junchul David Yoon, Hyunggee Kim, Sang-Hwan Hyun
Transgenic (TG) pigs are an important model for biomedical research, including disease modeling, pharmaceutical toxicity testing, and regenerative medicine. Here, we constructed 2 vector systems using the promoter of the pig glial fibrillary acidic protein (pGFAP) gene, which is an astrocyte cell marker. We established donor TG fibroblasts with pGFAP-CreERT2; LCMV-EGFPLoxP. We evaluated the effect of the transgenes on TG-SCNT embryo development. The cleavage rates were not significantly different among control and transgene-donor group...
December 28, 2017: Journal of Veterinary Science
https://www.readbyqxmd.com/read/29261807/characterization-of-host-proteins-interacting-with-the-lymphocytic-choriomeningitis-virus-l-protein
#6
Kseniya Khamina, Alexander Lercher, Michael Caldera, Christopher Schliehe, Bojan Vilagos, Mehmet Sahin, Lindsay Kosack, Anannya Bhattacharya, Peter Májek, Alexey Stukalov, Roberto Sacco, Leo C James, Daniel D Pinschewer, Keiryn L Bennett, Jörg Menche, Andreas Bergthaler
RNA-dependent RNA polymerases (RdRps) play a key role in the life cycle of RNA viruses and impact their immunobiology. The arenavirus lymphocytic choriomeningitis virus (LCMV) strain Clone 13 provides a benchmark model for studying chronic infection. A major genetic determinant for its ability to persist maps to a single amino acid exchange in the viral L protein, which exhibits RdRp activity, yet its functional consequences remain elusive. To unravel the L protein interactions with the host proteome, we engineered infectious L protein-tagged LCMV virions by reverse genetics...
December 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29212906/osteoblasts-are-rapidly-ablated-by-virus-induced-systemic-inflammation-following-lymphocytic-choriomeningitis-virus-or-pneumonia-virus-of-mice-infection-in-mice
#7
Steven Maltby, Alyssa J Lochrin, Bianca Bartlett, Hock L Tay, Jessica Weaver, Ingrid J Poulton, Maximilian W Plank, Helene F Rosenberg, Natalie A Sims, Paul S Foster
A link between inflammatory disease and bone loss is now recognized. However, limited data exist on the impact of virus infection on bone loss and regeneration. Bone loss results from an imbalance in remodeling, the physiological process whereby the skeleton undergoes continual cycles of formation and resorption. The specific molecular and cellular mechanisms linking virus-induced inflammation to bone loss remain unclear. In the current study, we provide evidence that infection of mice with either lymphocytic choriomeningitis virus (LCMV) or pneumonia virus of mice (PVM) resulted in rapid and substantial loss of osteoblasts from the bone surface...
December 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29196449/sustained-t-follicular-helper-cell-response-is-essential-for-control-of-chronic-viral-infection
#8
Ute Greczmiel, Nike Julia Kräutler, Alessandro Pedrioli, Ilka Bartsch, Paola Agnellini, Gregor Bedenikovic, James Harker, Kirsten Richter, Annette Oxenius
During chronic viral infections, both CD8 and CD4 T cell responses are functionally compromised. Alongside exhaustion of CD8 T cells during chronic viral infections, it has also been documented that the CD4 T cells have an increased propensity to differentiate toward CXCR5+ T follicular helper cell (TFH) lineage. Whether these TFH cells contribute to the immune response to chronic viral infection has remained unclear. Using chronic lymphocytic choriomeningitis virus (LCMV) infection in conjunction with an in vivo system where TFH cells can be conditionally ablated, we have established that these TFH cells do in fact play an important protective function...
December 1, 2017: Science Immunology
https://www.readbyqxmd.com/read/29187543/a-proteomic-survey-of-jun%C3%A3-n-virus-interactions-with-human-proteins-reveals-host-factors-required-for-arenavirus-replication
#9
Christopher M Ziegler, Philip Eisenhauer, Jamie A Kelly, Loan N Dang, Vedran Beganovic, Emily A Bruce, Benjamin R King, David J Shirley, Marion E Weir, Bryan A Ballif, Jason Botten
Arenaviruses are negative-strand, enveloped RNA viruses that cause significant human disease. In particular, Junín mammarenvirus (JUNV) is the etiologic agent of Argentine hemorrhagic fever. At present, little is known about the cellular proteins that the arenavirus matrix protein (Z) hijacks to accomplish its various functions, including driving the process of virus release. Further, there is a little knowledge regarding host proteins incorporated into arenavirus particles and their importance for virion function...
November 29, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29186689/lymphocytes-negatively-regulate-nk-cell-activity-via-qa-1b-following-viral-infection
#10
Haifeng C Xu, Jun Huang, Aleksandra A Pandyra, Elisabeth Lang, Yuan Zhuang, Christine Thöns, Jörg Timm, Dieter Häussinger, Marco Colonna, Harvey Cantor, Karl S Lang, Philipp A Lang
NK cells can reduce anti-viral T cell immunity during chronic viral infections, including infection with the lymphocytic choriomeningitis virus (LCMV). However, regulating factors that maintain the equilibrium between productive T cell and NK cell immunity are poorly understood. Here, we show that a large viral load resulted in inhibition of NK cell activation, which correlated with increased expression of Qa-1b, a ligand for inhibitory NK cell receptors. Qa-1b was predominantly upregulated on B cells following LCMV infection, and this upregulation was dependent on type I interferons...
November 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/29150240/dichotomous-expression-of-tnf-superfamily-ligands-on-antigen-presenting-cells-controls-post-priming-anti-viral-cd4-t-cell-immunity
#11
Yu-Han Chang, Kuan Chung Wang, Kuan-Lun Chu, Derek L Clouthier, Anh T Tran, Miguel S Torres Perez, Angela C Zhou, Ali A Abdul-Sater, Tania H Watts
T cell antigen-presenting cell (APC) interactions early during chronic viral infection are crucial for determining viral set point and disease outcome, but how and when different APC subtypes contribute to these outcomes is unclear. The TNF receptor superfamily (TNFRSF) member GITR is important for CD4+ T cell accumulation and control of chronic lymphocytic choriomeningitis virus (LCMV). We found that type I interferon (IFN-I) induced TNFSF ligands GITRL, 4-1BBL, OX40L, and CD70 predominantly on monocyte-derived APCs and CD80 and CD86 predominantly on classical dendritic cells (cDCs)...
November 21, 2017: Immunity
https://www.readbyqxmd.com/read/29140111/purging-exhausted-virus-specific-cd8-t-cell-phenotypes-by-somatic-cell-reprogramming
#12
Joshua Chan, Patrick Y Kim, Emiko Kranz, Yoshiko Nagaoka, YooJin Lee, Jing Wen, Heidi J Elsaesser, Meng Qin, David G Brooks, Gene-Errol Ringpis, Irvin S Y Chen, Masakazu Kamata
Cytotoxic T cells are critical in controlling virus infections. However, continuous antigen stimulation and negative regulatory factors cause CD8 T cells to enter a dysfunctional state (T cell exhaustion), resulting in viral persistence. We hypothesized that the exhausted T cell state could be molecularly rejuvenated using a somatic cell reprogramming technology, which is technically able to convert any types of cells to induced pluripotent stem cells (iPSCs), to regenerate functional T cells capable of purging chronic infection...
November 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29093652/semi-functional-quantitative-flow-cytometry-assay-for-lymphocytic-choriomeningitis-virus-titration
#13
Young Ho Ban, Sang-Jun Ha
Quantitative PCR and plaque assay are powerful virological techniques used to measure the load of defective or infectious virus in mouse and human. However, these methods display limitations such as cross contamination and long run-time. Here, we describe a novel technique termed as semi-functional quantitative flow cytometry (SFQF) for the accurate estimation of the quantity of infectious lymphocytic choriomeningitis virus (LCMV). LCMV titration method using flow cytometry was previously developed but has technical shortcomings, owing to the less optimized parameters such as cell overgrowth, plate scale, and detection threshold...
October 2017: Immune Network
https://www.readbyqxmd.com/read/29067678/the-immunoproteasome-subunit-lmp7-is-required-in-the-murine-thymus-for-filling-up-a-hole-in-the-t-cell-repertoire
#14
Michael Basler, Sarah Mundt, Marcus Groettrup
Cells of hematopoietic origin express high levels of the immunoproteasome, a cytokine-inducible variant of the proteasome which has been implicated in regulating inflammatory responses and antigen presentation. In the thymus, medullary thymic epithelial cells (mTECs) and cortical thymic epithelial cells (cTECs) do express different proteasome subunits exerting chymotrypsin-like activities suggesting distinct functions in thymic T cell selection. Employing the lymphocytic choriomeningitis virus (LCMV) infection model, we could show that the immunoproteasome subunit LMP7 was absolutely required for the generation of LCMV GP118-125 -specific T cells although the class I mediated presentation of GP118-125 was not dependent on LMP7...
October 24, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29060524/a-robust-beamforming-approach-for-early-detection-of-readiness-potential-with-application-to-brain-computer-interface-systems
#15
Maryam Mahmoodi, Bahador Makki Abadi, Hassan Khajepur, Mohammad Hossein Harirchian
Early detection of intention to move, at self-paced voluntary movements from the activities of neural current sources on the motor cortex, can be an effective approach to brain-computer interface (BCI) systems. Achieving high sensitivity and pre-movement negative latency are important issues for increasing the speed of BCI and other rehabilitation and neurofeedback systems used by disabled and stroke patients and helps enhance their movement abilities. Therefore, developing high-performance extractors or beamformers is a necessary task in this regard...
July 2017: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/29054998/interleukin-10-from-cd4-follicular-regulatory-t-cells-promotes-the-germinal-center-response
#16
Brian J Laidlaw, Yisi Lu, Robert A Amezquita, Jason S Weinstein, Jason A Vander Heiden, Namita T Gupta, Steven H Kleinstein, Susan M Kaech, Joe Craft
CD4+ follicular regulatory T (Tfr) cells suppress B cell responses through modulation of follicular helper T (Tfh) cells and germinal center (GC) development. We found that Tfr cells can also promote the GC response through provision of interleukin-10 (IL-10) after acute infection with lymphocytic choriomeningitis virus (LCMV). Sensing of IL-10 by B cells was necessary for optimal development of the GC response. GC B cells formed in the absence of Treg cell-derived IL-10 displayed an altered dark zone state and decreased expression of the transcription factor Forkhead box protein 1 (FOXO1)...
October 20, 2017: Science Immunology
https://www.readbyqxmd.com/read/29029641/sequence-specific-detection-of-different-strains-of-lcmv-in-a-single-sample-using-tentacle-probes
#17
Lina S Franco, Susan A Holechek, Michael R Caplan, Joseph N Blattman
BACKGROUND: Virus infections often result in quasispecies of viral strains that can have dramatic impacts on disease outcomes. However, sequencing of viruses to determine strain composition is time consuming and often cost-prohibitive. Rapid, cost-effective methods are needed for accurate measurement of virus diversity to understand virus evolution and can be useful for experimental systems. METHODS: We have developed a novel molecular method for sequence-specific detection of RNA virus genetic variants called Tentacle Probes...
October 13, 2017: Virology Journal
https://www.readbyqxmd.com/read/28993768/cd30-is-dispensable-for-t-cell-responses-to-influenza-virus-and-lymphocytic-choriomeningitis-virus-clone-13-but-contributes-to-age-associated-t-cell-expansion-in-mice
#18
Angela C Zhou, Laura M Snell, Michael E Wortzman, Tania H Watts
CD30 is a tumor necrosis factor receptor (TNFR) family member whose expression is associated with Hodgkin's disease, anaplastic large cell lymphomas, and other T and B lymphoproliferative disorders in humans. A limited number of studies have assessed the physiological role of CD30/CD30 ligand interactions in control of infection in mice. Here, we assess the role of CD30 in T-cell immunity to acute influenza and chronic lymphocytic choriomeningitis virus (LCMV) clone 13 infection, two viral infections in which other members of the TNFR superfamily are important for T-cell responses...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28986844/a-primary-human-liver-cell-culture-model-for-hemorrhagic-fever-viruses
#19
Mahmoud Djavani
Viral hemorrhagic fevers affect liver functions such as important metabolic processes and the replacement of new blood cells, coagulation factors, and growth factors. Typically, multi-organ diseases such as viral hemorrhagic fevers are studied in an organism, but it is also possible to derive information about the molecular events involved in disease processes by focusing on liver cell culture. Here we describe a multi-cell culture system that is capable of replicating the arenavirus LCMV-WE, a virus that can cause hemorrhagic fever in primates, as a model for liver infection by a hemorrhagic fever virus...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28986843/a-primate-model-for-viral-hemorrhagic-fever
#20
Maria S Salvato, Igor S Lukashevich, Yida Yang, Sandra Medina-Moreno, Mahmoud Djavani, Joseph Bryant, Juan David Rodas, Juan Carlos Zapata
Lymphocytic choriomeningitis virus strain WE (LCMV-WE), a Risk Group 3 virus, causes a disease in rhesus monkeys that closely resembles human infection with Lassa fever virus, a Risk Group 4 agent. Three stages of disease progression have been defined and profiled in this model: pre-viremic, viremic, and terminal. The earliest or pre-viremic stage reveals changes in the blood profile predictive of the later stages of disease. In order to identify whether specific changes are pathognomonic, it was necessary to perform a parallel infection with an attenuated virus (LCMV-Armstrong)...
2018: Methods in Molecular Biology
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