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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/28986841/murine-models-for-viral-hemorrhagic-fever
#11
Rosana Gonzalez-Quintial, Roberto Baccala
Hemorrhagic fever (HF) viruses, such as Lassa, Ebola, and dengue viruses, represent major human health risks due to their highly contagious nature, the severity of the clinical manifestations induced, the lack of vaccines, and the very limited therapeutic options currently available. Appropriate animal models are obviously critical to study disease pathogenesis and develop efficient therapies. We recently reported that the clone 13 (Cl13) variant of the lymphocytic choriomeningitis virus (LCMV-Cl13), a prototype arenavirus closely related to Lassa virus, causes in some mouse strains endothelial damage, vascular leakage, platelet loss, and death, mimicking pathological aspects typically observed in Lassa and other HF syndromes...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28978072/immunotherapy-of-wap-tnp-mice-with-early-stage-mammary-gland-tumors
#12
Michael Bruns, Wolfgang Deppert
The SV40 transgenic BALB/c mouse based WAP-T/WAP-TNP model for triple-negative breast cancer allows the analysis of parameters influencing immunotherapeutic approaches. Except for WAP-TNP tumors expressing the immune-dominant LCMV NP-epitope within SV40 T-antigen (T-AgNP) which is not expressed by T-Ag of WAP-T tumors, the tumors are extremely similar. Comparative anti-PD1/PD-L1 immunotherapy of WAP-T and WAP-TNP mice supported the hypothesis that the immunogenicity of tumor antigen T-cell epitopes strongly influences the success of immune checkpoint blockade therapy, with highly immunogenic T-cell epitopes favoring rapid CTL exhaustion...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28976562/seroprevalence-of-lymphocytic-choriomeningitis-virus-and-ljungan-virus-in-finnish-patients-with-suspected-neurological-infections
#13
Cristina Fevola, Suvi Kuivanen, Teemu Smura, Antti Vaheri, Hannimari Kallio-Kokko, Heidi C Hauffe, Olli Vapalahti, Anne J Jääskeläinen
BACKGROUND: Directly-transmitted rodent-borne zoonotic viruses, such as lymphocytic choriomeningitis virus (LCMV) can cause nervous system infections. Rodent-borne Ljungan virus (LV) is considered potentially zoonotic possibly causing neurological symptoms. Our objective was to understand the role of these two viruses compared to other pathogens in causing neurological infections in Finnish patients. METHODS: Routine screening data were available for 400 patients aged 5-50 years, collected from December 2013-December 2014 with suspected neurological infection...
October 4, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28949905/visualization-of-the-lymphocytic-choriomeningitis-mammarenavirus-lcmv-genome-reveals-the-early-endosome-as-a-possible-site-for-genome-replication-and-viral-particle-pre-assembly
#14
Benjamin R King, Samuel Kellner, Philip L Eisenhauer, Emily A Bruce, Christopher M Ziegler, Daniel Zenklusen, Jason William Botten
We report a fluorescence in situ hybridization (FISH) assay that allows the visualization of lymphocytic choriomeningitis mammarenavirus (LCMV) genomic RNAs in individual cells. We show that viral S segment genomic and antigenomic RNA, along with viral nucleoprotein, colocalize in subcellular structures we presume to be viral replication factories. These viral RNA structures are highly dynamic during acute infection, with the many small foci seen early coalescing into larger perinuclear foci later in infection...
September 27, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28948612/il-2-is-required-for-the-generation-of-viral-specific-cd4-th1-tissue-resident-memory-cells-and-b-cells-are-essential-for-maintenance-in-the-lung
#15
Brian D Hondowicz, Karen S Kim, Mikel J Ruterbusch, Gladys J Keitany, Marion Pepper
CD4(+) tissue resident cells are an important first line of defense against viral infections in the lungs and are critical for promoting the localization of lung resident CD8(+) T cells. However, relatively little is known about the signaling programs required for the development of viral-specific CD4(+) tissue resident cells in the lungs. Recently, it was shown that signaling through the high affinity IL-2 receptor is required for the differentiation of lung-resident Th2 memory (Trm) cells in a murine model of airway inflammation...
September 26, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28923314/a-simple-method-for-isolation-of-cell-associated-viral-particles-from-cell-culture
#16
Katarina Laposova, Ingrid Oveckova, Jana Tomaskova
A common method for cell-associated virus isolation involves disruption of infected cells by a combination of hypotonic burst, freeze-thaw cycles (F-T) and sonication. This protocol was also originally used for the preparation of cell-free extract containing the MX strain of lymphocytic choriomeningitis virus (LCMV), which is preferentially propagated by cell-to-cell contact and does not release distinct virions into the medium. In the present study, we compared different approaches to virus isolation. Based on virus yield, we show that deionized water lysis is the fastest and most effective method for releasing LCMV MX infectious viral particles from persistently infected cells...
November 2017: Journal of Virological Methods
https://www.readbyqxmd.com/read/28921501/immunological-tolerance-to-lcmv-antigens-differently-affects-control-of-acute-and-chronic-virus-infection-in-mice
#17
Christina Woopen, Tobias Straub, Oliver Schweier, Ulrike Aichele, Katharina Düker, Thomas Boehm, Hanspeter Pircher
Cytotoxic T lymphocytes (CTLs) play a key role in the control of lymphocytic choriomeningitis virus (LCMV) infection. In C57BL/6 mice (H-2(b) ), the CTL response is mainly directed against epitopes from the LCMV glycoprotein (GP) and the nucleoprotein (NP) which represent the two major viral proteins. The role of GP- versus NP-derived epitopes for viral clearance was examined using transgenic (tg) mice ubiquitously expressing LCMV GP and NP, respectively. These mice lack GP- or NP-specific CTLs and show decreased levels of GP- or NP-specific antibodies as a result of tolerance induction...
August 11, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28911907/microrna-22-controls-interferon-alpha-production-and-erythroid-maturation-in-response-to-infectious-stress-in-mice
#18
Claudine S Kadmon, Cameron T Landers, Haiyan S Li, Stephanie S Watowich, Antony Rodriguez, Katherine Y King
MicroRNA-22 (miR-22) is a highly conserved microRNA that can regulate cell proliferation, oncogenesis, and cell maturation, especially during stress. In hematopoietic stem cells (HSCs), miR-22 has been reported to be involved in the regulation of key self-renewal factors, including Tet2. Recent work demonstrates that miR-22 also participates in regulation of the interferon (IFN) response, and expression profiling studies suggest that it is variably expressed at different stages in erythroid differentiation...
December 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28900132/the-lipid-sensor-trem2-aggravates-disease-in-a-model-of-lcmv-induced-hepatitis
#19
Lindsay Kosack, Riem Gawish, Alexander Lercher, Bojan Vilagos, Anastasiya Hladik, Karin Lakovits, Anannya Bhattacharya, Christopher Schliehe, Ildiko Mesteri, Sylvia Knapp, Andreas Bergthaler
Lipid metabolism is increasingly being appreciated to affect immunoregulation, inflammation and pathology. In this study we found that mice infected with lymphocytic choriomeningitis virus (LCMV) exhibit global perturbations of circulating serum lipids. Mice lacking the lipid-sensing surface receptor triggering receptor expressed on myeloid cells 2 (Trem2 (-/-)) were protected from LCMV-induced hepatitis and showed improved virus control despite comparable virus-specific T cell responses. Non-hematopoietic expression of TREM2 was found to be responsible for aggravated hepatitis, indicating a novel role for TREM2 in the non-myeloid compartment...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28878077/irf9-prevents-cd8-t-cell-exhaustion-in-an-extrinsic-manner-during-acute-lymphocytic-choriomeningitis-virus-infection
#20
Magdalena Huber, Tamara Suprunenko, Thomas Ashhurst, Felix Marbach, Hartmann Raifer, Svenja Wolff, Thomas Strecker, Barney Viengkhou, So Ri Jung, Hannah-Lena Obermann, Stefan Bauer, Haifeng C Xu, Philipp A Lang, Adomati Tom, Karl S Lang, Nicholas J C King, Iain L Campbell, Markus J Hofer
Effective CD8(+) T cell responses play an important role in determining the course of a viral infection. Overwhelming antigen exposure can result in suboptimal CD8(+) T cell responses, leading to chronic infection. This altered CD8(+) T cell differentiation state, termed exhaustion, is characterized by reduced effector function, upregulation of inhibitory receptors, and altered expression of transcription factors. Prevention of overwhelming antigen exposure to limit CD8(+) T cell exhaustion is of significant interest for the control of chronic infection...
November 15, 2017: Journal of Virology
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