4,021 results match your criteria Lymphocytic Choriomeningitis


Oncolytic virotherapy enhances the efficacy of a cancer vaccine by modulating the tumor microenvironment.

Int J Cancer 2019 Apr 10. Epub 2019 Apr 10.

Division of Virology, Medical University of Innsbruck, Austria.

The efficacy of cancer vaccines has been limited by the immunosuppressive tumor microenvironment, which can be alleviated by immune checkpoint inhibitor (ICI) therapy. Here, we tested if oncolytic viruses, similar to ICI, can also synergize with cancer vaccines by modulating the tumor microenvironment. VSV-GP, a chimeric vesicular stomatitis virus (VSV) pseudotyped with the glycoprotein of the lymphocytic choriomeningitis virus, is a promising new oncolytic virus candidate. Read More

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http://dx.doi.org/10.1002/ijc.32325DOI Listing
April 2019
1 Read

Obesity Expands a Distinct Population of T Cells in Adipose Tissue and Increases Vulnerability to Infection.

Cell Rep 2019 Apr;27(2):514-524.e5

Department of Genetics, UNC-Chapel Hill School of Medicine, Chapel Hill, NC, USA; Department of Microbiology & Immunology, UNC-Chapel Hill School of Medicine, Chapel Hill, NC, USA. Electronic address:

Obesity in humans is associated with poorer health outcomes after infections compared with non-obese individuals. Here, we examined the effects of white adipose tissue and obesity on T cell responses to viral infection in mice. We show that lymphocytic choriomeningitis virus (LCMV) grows to high titer in adipose tissue. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.030DOI Listing

Inflation vs. Exhaustion of Antiviral CD8+ T-Cell Populations in Persistent Infections: Two Sides of the Same Coin?

Front Immunol 2019 6;10:197. Epub 2019 Mar 6.

Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.

Persistent virus infection can drive CD8+ T-cell responses which are markedly divergent in terms of frequency, phenotype, function, and distribution. On the one hand viruses such as Lymphocytic Choriomeningitis Virus (LCMV) Clone 13 can drive T-cell "exhaustion", associated with upregulation of checkpoint molecules, loss of effector functions, and diminished control of viral replication. On the other, low-level persistence of viruses such as Cytomegalovirus and Adenoviral vaccines can drive memory "inflation," associated with sustained populations of CD8+ T-cells over time, with maintained effector functions and a distinct phenotype. Read More

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http://dx.doi.org/10.3389/fimmu.2019.00197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6414785PMC
March 2019
1 Read

Infection drives meningeal engraftment by inflammatory monocytes that impairs CNS immunity.

Nat Immunol 2019 04 18;20(4):407-419. Epub 2019 Mar 18.

Viral Immunology and Intravital Imaging Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.

Tissue macrophages have an embryonic origin and can be replenished in some tissues under steady-state conditions by blood monocytes. However, little is known about the residency and properties of infiltrating monocytes after an inflammatory challenge. The meninges of the central nervous system (CNS) are populated by a dense network of macrophages that act as resident immune sentinels. Read More

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http://dx.doi.org/10.1038/s41590-019-0344-yDOI Listing
April 2019
1 Read

Lymphocytic Choriomeningitis Virus Infection Demonstrates Higher Replicative Capacity and Decreased Antiviral Response in the First-Trimester Placenta.

J Immunol Res 2019 7;2019:7375217. Epub 2019 Feb 7.

Department of Obstetrics and Gynecology, University of Texas Medical Branch, 301 University Blvd, Galveston, Texas, USA.

Lymphocytic choriomeningitis virus (LCMV) is a rodent disease that can be transmitted to humans. A majority of persons infected with LCMV have only minor symptoms; however, it can cross the placental barrier during pregnancy and cause congenital defects in the fetus. Some viral infections early in gestation are hypothesized to lead to worse outcomes compared to those acquired during late gestation; however, LCMV has not been studied in this context. Read More

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http://dx.doi.org/10.1155/2019/7375217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6383429PMC
February 2019
1 Read

The histone methyltransferase EZH2 primes the early differentiation of follicular helper T cells during acute viral infection.

Cell Mol Immunol 2019 Mar 6. Epub 2019 Mar 6.

Institute of Immunology, PLA, Third Military Medical University, 400038, Chongqing, China.

Epigenetic modifications to histones dictate the differentiation of naïve CD4 T cells into different subsets of effector T helper (T) cells. The histone methyltransferase enhancer of zeste homolog 2 (EZH2) has been implicated in the mechanism regulating the differentiation of T1, T2 and regulatory T (T) cells. However, whether and how EZH2 regulates follicular helper T (T) cell differentiation remain unknown. Read More

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http://dx.doi.org/10.1038/s41423-019-0219-zDOI Listing
March 2019
2 Reads
4.112 Impact Factor

The ubiquitin-like modifier FAT10 is required for normal IFN-γ production by activated CD8 T cells.

Mol Immunol 2019 Apr 25;108:111-120. Epub 2019 Feb 25.

Division of Immunology, Department of Biology, University of Konstanz, 78457 Konstanz, Germany; Biotechnology Institute Thurgau at the University of Konstanz, 8280 Kreuzlingen, Switzerland. Electronic address:

FAT10 is the only ubiquitin-like modifier which directly targets its substrate proteins for rapid degradation by the proteasome. While the conjugation and proteasomal targeting of FAT10 are fairly well understood, the biological functions of FAT10 have remained largely elusive. Here we have investigated the role of FAT10 in cytokine responses in mice upon viral infection. Read More

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http://dx.doi.org/10.1016/j.molimm.2019.02.010DOI Listing
April 2019
2 Reads

Sustained Type I Interferon Reinforces NK Cell-Mediated Cancer Immunosurveillance during Chronic Virus Infection.

Cancer Immunol Res 2019 Apr 26;7(4):584-599. Epub 2019 Feb 26.

Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.

The importance of natural killer (NK) cells in the early immune response to viral or bacterial infection is well known. However, the phenotype, function, and physiologic role of NK cells during the late stage of persistent viral infection have not been extensively studied. Here, we characterized NK cells in mice persistently infected with lymphocytic choriomeningitis virus clone 13 and showed that in contrast to NK cells from acutely infected or uninfected mice, NK cells from chronically infected mice expressed a terminally differentiated phenotype, stronger cytotoxicity, and reduced inhibitory receptor expression. Read More

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http://dx.doi.org/10.1158/2326-6066.CIR-18-0403DOI Listing
April 2019
7 Reads

Enhancing immunity prevents virus-induced T-cell-mediated immunopathology in B cell-deficient mice.

Eur J Immunol 2019 Feb 22. Epub 2019 Feb 22.

Institute for Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.

Hyper-activated or deviated immune responses can result in immunopathological diseases. Paradoxically, immunodeficiency represents a frequent cause of such immune-mediated pathologies. Immunopathological manifestations are commonly treated by immunosuppression, but in situations in which immunodeficiency is the basis of disease development, enhancing immunity may represent an alternative treatment option. Read More

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http://dx.doi.org/10.1002/eji.201847962DOI Listing
February 2019

Complexities of Type I Interferon Biology: Lessons from LCMV.

Viruses 2019 Feb 20;11(2). Epub 2019 Feb 20.

School of Life and Environmental Sciences, the Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, and the Bosch Institute, The University of Sydney, Sydney, NSW 2006, Australia.

Over the past decades, infection of mice with lymphocytic choriomeningitis virus (LCMV) has provided an invaluable insight into our understanding of immune responses to viruses. In particular, this model has clarified the central roles that type I interferons play in initiating and regulating host responses. The use of different strains of LCMV and routes of infection has allowed us to understand how type I interferons are critical in controlling virus replication and fostering effective antiviral immunity, but also how they promote virus persistence and functional exhaustion of the immune response. Read More

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http://dx.doi.org/10.3390/v11020172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409748PMC
February 2019

Immune Exhaustion: Past Lessons and New Insights from Lymphocytic Choriomeningitis Virus.

Viruses 2019 Feb 13;11(2). Epub 2019 Feb 13.

Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

Lymphocytic choriomeningitis virus (LCMV) is a paradigm-forming experimental system with a remarkable track record of contributing to the discovery of many of the fundamental concepts of modern immunology. The ability of LCMV to establish a chronic infection in immunocompetent adult mice was instrumental for identifying T cell exhaustion and this system has been invaluable for uncovering the complexity, regulators, and consequences of this state. These findings have been directly relevant for understanding why ineffective T cell responses commonly arise during many chronic infections including HIV and HCV, as well as during tumor outgrowth. Read More

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http://dx.doi.org/10.3390/v11020156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410286PMC
February 2019

A functional subset of CD8 T cells during chronic exhaustion is defined by SIRPα expression.

Nat Commun 2019 02 15;10(1):794. Epub 2019 Feb 15.

Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, Hamilton, MT, 59840, USA.

Prolonged exposure of CD8 T cells to antigenic stimulation, as in chronic viral infections, leads to a state of diminished function termed exhaustion. We now demonstrate that even during exhaustion there is a subset of functional CD8 T cells defined by surface expression of SIRPα, a protein not previously reported on lymphocytes. On SIRPα CD8 T cells, expression of co-inhibitory receptors is counterbalanced by expression of co-stimulatory receptors and it is only SIRPα cells that actively proliferate, transcribe IFNγ and show cytolytic activity. Read More

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http://dx.doi.org/10.1038/s41467-019-08637-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6377614PMC
February 2019
4 Reads

Induction of Tier 1 HIV Neutralizing Antibodies by Envelope Trimers Incorporated into a Replication Competent Vesicular Stomatitis Virus Vector.

Viruses 2019 Feb 15;11(2). Epub 2019 Feb 15.

Division of Virology, Medical University of Innsbruck, 6020 Innsbruck, Austria.

A chimeric vesicular stomatitis virus with the glycoprotein of the lymphocytic choriomeningitis virus, VSV-GP, is a potent viral vaccine vector that overcomes several of the limitations of wild-type VSV. Here, we evaluated the potential of VSV-GP as an HIV vaccine vector. We introduced genes for different variants of the HIV-1 envelope protein Env, i. Read More

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http://dx.doi.org/10.3390/v11020159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409518PMC
February 2019
2 Reads

Choline acetyltransferase-expressing T cells are required to control chronic viral infection.

Science 2019 02;363(6427):639-644

The Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada.

Although widely studied as a neurotransmitter, T cell-derived acetylcholine (ACh) has recently been reported to play an important role in regulating immunity. However, the role of lymphocyte-derived ACh in viral infection is unknown. Here, we show that the enzyme choline acetyltransferase (ChAT), which catalyzes the rate-limiting step of ACh production, is robustly induced in both CD4 and CD8 T cells during lymphocytic choriomeningitis virus (LCMV) infection in an IL-21-dependent manner. Read More

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http://dx.doi.org/10.1126/science.aau9072DOI Listing
February 2019
1 Read

TLR4 signaling improves PD-1 blockade therapy during chronic viral infection.

PLoS Pathog 2019 02 6;15(2):e1007583. Epub 2019 Feb 6.

Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States of America.

CD8 T cells are necessary for the elimination of intracellular pathogens, but during chronic viral infections, CD8 T cells become exhausted and unable to control the persistent infection. Programmed cell death-1 (PD-1) blockade therapies have been shown to improve CD8 T cell responses during chronic viral infections. These therapies have been licensed to treat cancers in humans, but they have not yet been licensed to treat chronic viral infections because limited benefit is seen in pre-clinical animal models of chronic infection. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6380600PMC
February 2019
3 Reads

Liver-Resident NK Cells Control Antiviral Activity of Hepatic T Cells via the PD-1-PD-L1 Axis.

Immunity 2019 Feb 29;50(2):403-417.e4. Epub 2019 Jan 29.

Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China; Institue of Immunology, University of Science and Technology of China, Hefei, Anhui 230027, China. Electronic address:

The tolerogenic microenvironment of the liver is associated with impaired hepatic T cell function. Here, we examined the contribution of liver-resident natural killer (LrNK) cells, a prominent hepatic NK cell compartment, to T cell antiviral responses in the liver. The number of virus-specific T cells increased in LrNK-cell-deficient mice during both acute and chronic lymphocytic choriomeningitis virus infection. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10747613183057
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http://dx.doi.org/10.1016/j.immuni.2018.12.024DOI Listing
February 2019
21 Reads

Viruses Teaching Immunology: Role of LCMV Model and Human Viral Infections in Immunological Discoveries.

Viruses 2019 Jan 27;11(2). Epub 2019 Jan 27.

Penn Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Virology has played an essential role in deciphering many immunological phenomena, thus shaping our current understanding of the immune system. Animal models of viral infection and human viral infections were both important tools for immunological discoveries. This review discusses two immunological breakthroughs originally identified with the help of the lymphocytic choriomeningitis virus (LCMV) model; immunological restriction by major histocompatibility complex and immunotherapy using checkpoint blockade. Read More

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http://dx.doi.org/10.3390/v11020106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410308PMC
January 2019

Macrophage IFN-I signaling promotes autoreactive T cell infiltration into islets in type 1 diabetes model.

JCI Insight 2019 Jan 24;4(2). Epub 2019 Jan 24.

Here, we report a pathogenic role for type I IFN (IFN-I) signaling in macrophages, and not β cells in the islets, for the development of type 1 diabetes (T1D). Following lymphocytic choriomeningitis (LCMV) infection in the Rip-LCMV-GP T1D model, macrophages accumulated near islets and in close contact to islet-infiltrating GP-specific (autoimmune) CD8+ T cells. Depletion of macrophages with clodronate liposomes or genetic ablation of Ifnar in macrophages aborted T1D, despite proliferation of GP-specific (autoimmune) CD8+ T cells. Read More

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http://dx.doi.org/10.1172/jci.insight.125067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413832PMC
January 2019

Chemokine Expression in Murine RPE/Choroid in Response to Systemic Viral Infection and Elevated Levels of Circulating Interferon-γ.

Invest Ophthalmol Vis Sci 2019 Jan;60(1):192-201

University of Copenhagen, Faculty of Health and Medical Sciences, Department of Immunology and Microbiology, Copenhagen, Denmark.

Purpose: To examine how circulating immune mediators in vivo may affect gene and protein expression at the RPE/choroid interface.

Methods: Young mice were systemically infected with lymphocytic choriomeningitis virus (LCMV) or continuously infused with IFN-γ. RPE/choroid was isolated and analyzed with whole-transcriptome gene expression microarrays. Read More

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http://dx.doi.org/10.1167/iovs.18-25721DOI Listing
January 2019

Simultaneous rapid detection of Hantaan virus and Seoul virus using RT-LAMP in rats.

PeerJ 2019 8;6:e6068. Epub 2019 Jan 8.

Institute of Biological Sciences, Jinzhou Medical University, Jinzhou, Liaoning, China.

Background: Hemorrhagic fever with renal syndrome is in most cases caused by the Hantaan virus (HTNV) and Seoul virus (SEOV). To develop and apply reverse transcription loop-mediated isothermal amplification (RT-LAMP) to detect HTNV and SEOV simultaneously, which was faster, more cost effective, and easier to perform as the target gene amplified rapidly. In this article an assay based on LAMP is demonstrated, which only employs such apparatus as a water bath or a heat block. Read More

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http://dx.doi.org/10.7717/peerj.6068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6329334PMC
January 2019
1 Read

CD47 Expression in Natural Killer Cells Regulates Homeostasis and Modulates Immune Response to Lymphocytic Choriomeningitis Virus.

Front Immunol 2018 20;9:2985. Epub 2018 Dec 20.

Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.

CD47 is a ubiquitous cell surface receptor that directly regulates T cell immunity by interacting with its inhibitory ligand thrombospondin-1 and limits clearance of cells by phagocytes that express its counter-receptor signal-regulatory protein-α. Murine natural killer (NK) cells express higher levels of CD47 than other lymphocytes, but the role of CD47 in regulating NK cell homeostasis and immune function remains unclear. mice exhibited depletion of NK precursors in bone marrow, consistent with the antiphagocytic function of CD47. Read More

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http://dx.doi.org/10.3389/fimmu.2018.02985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320676PMC
December 2018
6 Reads

Expression of novel long noncoding RNAs defines virus-specific effector and memory CD8 T cells.

Nat Commun 2019 01 14;10(1):196. Epub 2019 Jan 14.

Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, 30307, USA.

In response to viral infection, CD8 T cells undergo expansion and differentiate into distinct classes of effector cells. After clearance of the virus, a small population of long-lived memory cells persists. Comprehensive studies have defined the protein-coding transcriptional changes associated with this process. Read More

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http://dx.doi.org/10.1038/s41467-018-07956-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331603PMC
January 2019
1 Read

Residual LCMV antigen in transiently CD4 T cell-depleted mice induces high levels of virus-specific antibodies but only limited B-cell memory.

Eur J Immunol 2019 Apr 4;49(4):626-637. Epub 2019 Feb 4.

Institute for Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.

Infection of C57BL/6 mice with lymphocytic choriomeningitis virus (LCMV) strain Armstrong (Arm) induces an acute infection with rapid virus clearance by CD8 T cells independently of CD4 T cell help. Residual viral antigen may, however, persist for a prolonged time. Here, we demonstrate that mice that had been transiently depleted of CD4 T cells during acute LCMV Arm infection generated high levels of virus-specific IgG antibodies (Ab) after viral clearance. Read More

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http://dx.doi.org/10.1002/eji.201847772DOI Listing
April 2019
5 Reads

Circumventricular Organs and Parasite Neurotropism: Neglected Gates to the Brain?

Front Immunol 2018 11;9:2877. Epub 2018 Dec 11.

Department Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.

Circumventricular organs (CVOs), neural structures located around the third and fourth ventricles, harbor, similarly to the choroid plexus, vessels devoid of a blood-brain barrier (BBB). This enables them to sense immune-stimulatory molecules in the blood circulation, but may also increase chances of exposure to microbes. In spite of this, attacks to CVOs by microbes are rarely described. Read More

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https://www.frontiersin.org/article/10.3389/fimmu.2018.02877
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http://dx.doi.org/10.3389/fimmu.2018.02877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6302769PMC
December 2018
12 Reads

Cutting Edge: Early Attrition of Memory T Cells during Inflammation and Costimulation Blockade Is Regulated Concurrently by Proapoptotic Proteins Fas and Bim.

J Immunol 2019 Feb 4;202(3):647-651. Epub 2019 Jan 4.

Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605;

Apoptosis of CD8 T cells is an essential mechanism that maintains immune system homeostasis, prevents autoimmunity, and reduces immunopathology. CD8 T cell death also occurs early during the response to both inflammation and costimulation blockade (CoB). In this article, we studied the effects of a combined deficiency of Fas (extrinsic pathway) and Bim (intrinsic pathway) on early T cell attrition in response to lymphocytic choriomeningitis virus infection and during CoB during transplantation. Read More

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http://dx.doi.org/10.4049/jimmunol.1800278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344249PMC
February 2019
1 Read

IFN-γ and CD25 drive distinct pathologic features during hemophagocytic lymphohistiocytosis.

J Allergy Clin Immunol 2018 Dec 19. Epub 2018 Dec 19.

VIB Center for Brain & Disease Research, Leuven, Belgium; KU Leuven-University of Leuven, Department of Microbiology and Immunology, Leuven, Belgium. Electronic address:

Background: Inflammatory activation of CD8 T cells can, when left unchecked, drive severe immunopathology. Hyperstimulation of CD8 T cells through a broad set of triggering signals can precipitate hemophagocytic lymphohistiocytosis (HLH), a life-threatening systemic inflammatory disorder.

Objective: The mechanism linking CD8 T-cell hyperactivation to pathology is controversial, with excessive production of IFN-γ and, more recently, excessive consumption of IL-2, which are proposed as competing hypotheses. Read More

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http://dx.doi.org/10.1016/j.jaci.2018.10.068DOI Listing
December 2018

The Innate Immune Sensor NLRC3 Acts as a Rheostat that Fine-Tunes T Cell Responses in Infection and Autoimmunity.

Immunity 2018 Dec;49(6):1049-1061.e6

Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address:

Appropriate immune responses require a fine balance between immune activation and attenuation. NLRC3, a non-inflammasome-forming member of the NLR innate immune receptor family, attenuates inflammation in myeloid cells and proliferation in epithelial cells. T lymphocytes express the highest amounts of Nlrc3 transcript where its physiologic relevance is unknown. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10747613183044
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http://dx.doi.org/10.1016/j.immuni.2018.10.008DOI Listing
December 2018
40 Reads

Metal chelators for the inhibition of the lymphocytic choriomeningitis virus endonuclease domain.

Antiviral Res 2019 Feb 14;162:79-89. Epub 2018 Dec 14.

Aix-Marseille Université, CNRS UMR 7257, Architecture et Fonction des Macromolécules Biologiques, 163 avenue de Luminy, 13288, Marseille, France. Electronic address:

Arenaviridae is a viral family whose members are associated with rodent-transmitted infections to humans responsible of severe diseases. The current lack of a vaccine and limited therapeutic options make the development of efficacious drugs of high priority. The cap-snatching mechanism of transcription of Arenavirus performed by the endonuclease domain of the L-protein is unique and essential, so we developed a drug design program targeting the endonuclease activity of the prototypic Lymphocytic ChorioMeningitis Virus. Read More

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http://dx.doi.org/10.1016/j.antiviral.2018.12.008DOI Listing
February 2019
3 Reads

Aging of Antiviral CD8 Memory T Cells Fosters Increased Survival, Metabolic Adaptations, and Lymphoid Tissue Homing.

J Immunol 2019 Jan 14;202(2):460-475. Epub 2018 Dec 14.

Department of Anesthesiology, University of Colorado Denver, Aurora, CO 80045;

Aging of established antiviral T cell memory can foster a series of progressive adaptations that paradoxically improve rather than compromise protective CD8 T cell immunity. We now provide evidence that this gradual evolution, the pace of which is contingent on the precise context of the primary response, also impinges on the molecular mechanisms that regulate CD8 memory T cell (T) homeostasis. Over time, CD8 T generated in the wake of an acute infection with the natural murine pathogen lymphocytic choriomeningitis virus become more resistant to apoptosis and acquire enhanced cytokine responsiveness without adjusting their homeostatic proliferation rates; concurrent metabolic adaptations promote increased CD8 T quiescence and fitness but also impart the reacquisition of a partial effector-like metabolic profile; and a gradual redistribution of aging CD8 T from blood and nonlymphoid tissues to lymphatic organs results in CD8 T accumulations in bone marrow, splenic white pulp, and, particularly, lymph nodes. Read More

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http://dx.doi.org/10.4049/jimmunol.1801277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358025PMC
January 2019

Cell-to-cell transmission of lymphocytic choriomeningitis virus MX strain during persistent infection and its influence on cell migration.

Acta Virol 2018;62(4):424-434

Lymphocytic choriomeningitis virus (LCMV) can establish in its host a persistent infection, without any prominent symptoms. Even during this infection, when the infectious virions are not released, the virus still disseminates effectively. A very effective and fast way of infection of neighboring cells utilized by many viruses is cell-to-cell transmission. Read More

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http://www.elis.sk/index.php?page=shop.product_details&f
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http://dx.doi.org/10.4149/av_2018_411DOI Listing
April 2019
10 Reads

Is This Organ Donor Safe?: Donor-Derived Infections in Solid Organ Transplantation.

Authors:
Staci A Fischer

Surg Clin North Am 2019 Feb;99(1):117-128

The Warren Alpert Medical School of Brown University, 222 Richmond Street, Providence, RI 02903, USA; Accreditation Council for Graduate Medical Education, 401 North Michigan Avenue, Suite 2000, Chicago, IL 60611, USA. Electronic address:

Infection is an inevitable complication of solid organ transplantation. Unrecognized infection may be transmitted from a donor and result in disseminated disease in the immunosuppressed host. Recent outbreaks of deceased donor-derived infections resulting in high rates of mortality and severe morbidity have emphasized the need to be cautious in using donors with possible meningoencephalitis. Read More

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http://dx.doi.org/10.1016/j.suc.2018.09.009DOI Listing
February 2019
1 Read

High Constitutive Interleukin 10 Level Interferes With the Immune Response to Varicella-Zoster Virus in Elderly Recipients of Live Attenuated Zoster Vaccine.

J Infect Dis 2019 Apr;219(8):1338-1346

Department of Pathology and Cell Biology, Columbia University Vagelos College of Physicians and Surgeons, New York, New York.

Introduction: Live attenuated zoster vaccine (Zostavax) was used to test the hypothesis that constitutive level of interleukin 10 (IL-10), which may be high in elderly subjects, impairs vaccine efficacy. If constitutive IL-10 impairs vaccine efficacy, the effectiveness of viral vaccines might be improved by transient inhibition of IL-10 before vaccination.

Methods: Zostavax was given to 26 patients (age, 60-80 years). Read More

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http://dx.doi.org/10.1093/infdis/jiy660DOI Listing
April 2019
12 Reads

Mechanisms of lymphatic system-specific viral replication and its potential role in autoimmune disease.

Clin Exp Immunol 2019 Jan;195(1):64-73

University of Duisburg-Essen, Institute of Immunology, Medical Faculty, Essen, Germany.

Viral infections can be fatal because of the direct cytopathic effects of the virus or the induction of a strong, uncontrolled inflammatory response. Virus and host intrinsic characteristics strongly modulate the outcome of viral infections. Recently we determined the circumstances under which enhanced replication of virus within the lymphoid tissue is beneficial for the outcome of a disease. Read More

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http://doi.wiley.com/10.1111/cei.13241
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http://dx.doi.org/10.1111/cei.13241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6300653PMC
January 2019
6 Reads

Evaluation of the capacities of mouse TCR profiling from short read RNA-seq data.

PLoS One 2018 15;13(11):e0207020. Epub 2018 Nov 15.

Regeneron Pharmaceuticals, Tarrytown, New York, United States of America.

Profiling T cell receptor (TCR) repertoire via short read transcriptome sequencing (RNA-Seq) has a unique advantage of probing simultaneously TCRs and the genome-wide RNA expression of other genes. However, compared to targeted amplicon approaches, the shorter read length is more prone to mapping error. In addition, only a small percentage of the genome-wide reads may cover the TCR loci and thus the repertoire could be significantly under-sampled. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0207020PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6237323PMC
April 2019
20 Reads

Selective blockade of the lyso-PS lipase ABHD12 stimulates immune responses in vivo.

Nat Chem Biol 2018 12 12;14(12):1099-1108. Epub 2018 Nov 12.

Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA.

ABHD12 metabolizes bioactive lysophospholipids, including lysophosphatidylserine (lyso-PS). Deleterious mutations in human ABHD12 cause the neurological disease PHARC, and ABHD12 mice display PHARC-like phenotypes, including hearing loss, along with elevated brain lyso-PS and features of stimulated innate immune cell function. Here, we develop a selective and in vivo-active inhibitor of ABHD12 termed DO264 and show that this compound elevates lyso-PS in mouse brain and primary human macrophages. Read More

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http://www.nature.com/articles/s41589-018-0155-8
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http://dx.doi.org/10.1038/s41589-018-0155-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6263940PMC
December 2018
32 Reads

Viral Encephalitis.

Neurol Clin 2018 Nov 20;36(4):705-724. Epub 2018 Sep 20.

Division of Neuroimmunology and Neuroinfectious Diseases, Department of Neurology, Johns Hopkins Encephalitis Center, Johns Hopkins University School of Medicine, 600 N Wolfe Street, Baltimore, MD 21287, USA.

Viruses are a frequent cause of encephalitis. Common or important viruses causing encephalitis include herpesviruses, arboviruses, enteroviruses, parechoviruses, mumps, measles, rabies, Ebola, lymphocytic choriomeningitis virus, and henipaviruses. Other viruses may cause an encephalopathy. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S07338619183124
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http://dx.doi.org/10.1016/j.ncl.2018.07.001DOI Listing
November 2018
25 Reads

Lymphocytic choriomeningitis virus meningoencephalitis in a renal transplant recipient following exposure to mice.

Transpl Infect Dis 2018 Dec 5;20(6):e13013. Epub 2018 Nov 5.

Division of Infectious Disease, St. John Hospital and Medical Center, Grosse Pointe Woods, Michigan.

Solid organ transplant recipients (SOTR) are at increased risk for a wide variety of typical and atypical infections as a consequence of impaired cell mediated and humoral immunity. We report a case of meningoencephalitis in a renal transplant recipient caused by lymphocytic choriomeningitis virus (LCMV) acquired by exposure to mice excreta. The clinical course was complicated by the development of hydrocephalus, requiring a ventriculoperitoneal shunt. Read More

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http://dx.doi.org/10.1111/tid.13013DOI Listing
December 2018
3 Reads

CD8 T Cell Priming in Established Chronic Viral Infection Preferentially Directs Differentiation of Memory-like Cells for Sustained Immunity.

Immunity 2018 10 9;49(4):678-694.e5. Epub 2018 Oct 9.

Princess Margaret Cancer Center, University Health Network, Toronto, ON, M5G 2M9 Canada; Department of Immunology, University of Toronto, Toronto, ON, M5S 1A8 Canada. Electronic address:

CD8 T cell exhaustion impedes control of chronic viral infection; yet how new T cell responses are mounted during chronic infection is unclear. Unlike T cells primed at the onset of infection that rapidly differentiate into effectors and exhaust, we demonstrate that virus-specific CD8 T cells primed after establishment of chronic LCMV infection preferentially generate memory-like transcription factor TCF1 cells that were transcriptionally and proteomically distinct, less exhausted, and more responsive to immunotherapy. Mechanistically, adaptations of antigen-presenting cells and diminished T cell signaling intensity promoted differentiation of the memory-like subset at the expense of rapid effector cell differentiation, which was now highly dependent on IL-21-mediated CD4 T cell help for its functional generation. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10747613183034
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http://dx.doi.org/10.1016/j.immuni.2018.08.002DOI Listing
October 2018
35 Reads

Bacterial coinfection restrains antiviral CD8 T-cell response via LPS-induced inhibitory NK cells.

Nat Commun 2018 10 8;9(1):4117. Epub 2018 Oct 8.

Institute for Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.

Infection of specific pathogen-free mice with lymphocytic choriomeningitis virus (LCMV) is a widely used model to study antiviral T-cell immunity. Infections in the real world, however, are often accompanied by coinfections with unrelated pathogens. Here we show that in mice, systemic coinfection with E. Read More

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http://www.nature.com/articles/s41467-018-06609-z
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http://dx.doi.org/10.1038/s41467-018-06609-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6175863PMC
October 2018
13 Reads

The Kinase Activity of Hematopoietic Progenitor Kinase 1 Is Essential for the Regulation of T Cell Function.

Cell Rep 2018 Oct;25(1):80-94

Genentech, 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address:

We examined hematopoietic protein kinase 1 (HPK1), whose reliance on scaffold versus kinase functions for negative immune cell regulation is poorly understood and critical to its assessment as a viable drug target. We identify kinase-dependent roles for HPK1 in CD8 T cells that restrict their anti-viral and anti-tumor responses by using HPK1 kinase-dead (HPK1.kd) knockin mice. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S22111247183144
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http://dx.doi.org/10.1016/j.celrep.2018.09.012DOI Listing
October 2018
15 Reads

The Transcription Factor Runx2 Is Required for Long-Term Persistence of Antiviral CD8 Memory T Cells.

Immunohorizons 2018 Aug;2(7):251-261

Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01605.

During acute lymphocytic choriomeningitis virus infection, pathogen-specific CD8 cytotoxic T lymphocytes undergo clonal expansion leading to viral clearance. Following this, the majority of pathogen-specific CD8 T cells undergo apoptosis, leaving a small number of memory CD8 T cells that persist long-term and provide rapid protection upon secondary infection. Whereas much is known about the cytokines and transcription factors that regulate the early effector phase of the antiviral CD8 T cell response, the factors regulating memory T cell homeostasis and survival are not well understood. Read More

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http://dx.doi.org/10.4049/immunohorizons.1800046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156005PMC
August 2018
1 Read

Enhancing FcγR-mediated antibody effector function during persistent viral infection.

Sci Immunol 2018 Sep;3(27)

Emory Vaccine Center, Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.

Persistent viral infections can interfere with FcγR-mediated antibody effector functions by excessive immune complex (IC) formation, resulting in resistance to therapeutic FcγR-dependent antibodies. We and others have previously demonstrated that mice persistently infected with lymphocytic choriomeningitis virus (LCMV) are resistant to a wide range of depleting antibodies due to excessive IC formation. Here, we dissect the mechanisms by which two depleting antibodies overcome the obstacle of endogenous ICs and achieve efficient target cell depletion in persistently infected mice. Read More

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http://dx.doi.org/10.1126/sciimmunol.aao3125DOI Listing
September 2018
7 Reads

Lupus acceleration by a MAVS-activating RNA virus requires endosomal TLR signaling and host genetic predisposition.

PLoS One 2018 10;13(9):e0203118. Epub 2018 Sep 10.

Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, United States of America.

Viruses have long been implicated in the pathogenesis of autoimmunity, yet their contribution remains circumstantial partly due to the lack of well-documented information on infections prior to autoimmune disease onset. Here, we used the lymphocytic choriomeningitis virus (LCMV) as a model to mechanistically dissect the impact of viral infection on lupus-like autoimmunity. Virus persistence strongly enhanced disease in mice with otherwise weak genetic predisposition but not in highly predisposed or non-autoimmune mice, indicating a synergistic interplay between genetic susceptibility and virus infection. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203118PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6130858PMC
February 2019
8 Reads

Is This Organ Donor Safe?: Donor-Derived Infections in Solid Organ Transplantation.

Authors:
Staci A Fischer

Infect Dis Clin North Am 2018 09;32(3):495-506

The Warren Alpert Medical School of Brown University, 222 Richmond Street, Providence, RI 02903, USA; Accreditation Council for Graduate Medical Education, 401 North Michigan Avenue, Suite 2000, Chicago, IL 60611, USA. Electronic address:

Infection is an inevitable complication of solid organ transplantation. Unrecognized infection may be transmitted from a donor and result in disseminated disease in the immunosuppressed host. Recent outbreaks of deceased donor-derived infections resulting in high rates of mortality and severe morbidity have emphasized the need to be cautious in using donors with possible meningoencephalitis. Read More

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http://dx.doi.org/10.1016/j.idc.2018.04.001DOI Listing
September 2018
7 Reads

Local synthesis of immunosuppressive glucocorticoids in the intestinal epithelium regulates anti-viral immune responses.

Cell Immunol 2018 Dec 18;334:1-10. Epub 2018 Aug 18.

Biochemical Pharmacology, Department of Biology, University of Konstanz, Germany. Electronic address:

The nuclear receptor Small Heterodimer Partner (SHP) is a transcriptional target and inhibitor of Liver Receptor Homolog 1 (LRH-1), the transcriptional regulator of intestinal glucocorticoid (GC) synthesis. The role of SHP in the regulation of intestinal GC synthesis and its impact on T cell-mediated anti-viral immune responses in the intestinal mucosa are currently not understood. Lymphocytic choriomeningitis virus (LCMV) infection promoted intestinal GC synthesis, which was enhanced in SHP-deficient mice. Read More

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http://dx.doi.org/10.1016/j.cellimm.2018.08.009DOI Listing
December 2018
12 Reads

Lack of Sprouty 1 and 2 enhances survival of effector CD8 T cells and yields more protective memory cells.

Proc Natl Acad Sci U S A 2018 09 20;115(38):E8939-E8947. Epub 2018 Aug 20.

Virology and Immunology, Gladstone Institutes, San Francisco, CA 94158;

Identifying novel pathways that promote robust function and longevity of cytotoxic T cells has promising potential for immunotherapeutic strategies to combat cancer and chronic infections. We show that sprouty 1 and 2 (Spry1/2) molecules regulate the survival and function of memory CD8 T cells. Spry1/2 double-knockout (DKO) ovalbumin (OVA)-specific CD8 T cells (OT-I cells) mounted more vigorous autoimmune diabetes than WT OT-I cells when transferred to mice expressing OVA in their pancreatic β-islets. Read More

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http://dx.doi.org/10.1073/pnas.1808320115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156615PMC
September 2018
4 Reads

Cholestasis induced liver pathology results in dysfunctional immune responses after arenavirus infection.

Sci Rep 2018 Aug 15;8(1):12179. Epub 2018 Aug 15.

Department of Molecular Medicine II, Medical Faculty, Heinrich Heine University, Universitätsstrasse. 1, 40225, Düsseldorf, Germany.

Immune responses are critical for defense against pathogens. However, prolonged viral infection can result in defective T cell immunity, leading to chronic viral infection. We studied immune activation in response to arenavirus infection during cholestasis using bile duct ligation (BDL). Read More

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http://dx.doi.org/10.1038/s41598-018-30627-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6093869PMC
August 2018
7 Reads

Lymphocytic choriomeningitis virus Clone 13 infection causes either persistence or acute death dependent on IFN-1, cytotoxic T lymphocytes (CTLs), and host genetics.

Proc Natl Acad Sci U S A 2018 08 30;115(33):E7814-E7823. Epub 2018 Jul 30.

Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037.

Understanding of T cell exhaustion and successful therapy to restore T cell function was first described using Clone (Cl) 13 variant selected from the lymphocytic choriomeningitis virus (LCMV) Armstrong (ARM) 53b parental strain. T cell exhaustion plays a pivotal role in both persistent infections and cancers of mice and humans. C57BL/6, BALB, SWR/J, A/J, 129, C3H, and all but one collaborative cross (CC) mouse strain following Cl 13 infection have immunosuppressed T cell responses, high PD-1, and viral titers leading to persistent infection and normal life spans. Read More

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http://dx.doi.org/10.1073/pnas.1804674115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6099862PMC
August 2018
29 Reads

PD-1 Inhibitory Receptor Downregulates Asparaginyl Endopeptidase and Maintains Foxp3 Transcription Factor Stability in Induced Regulatory T Cells.

Immunity 2018 08 24;49(2):247-263.e7. Epub 2018 Jul 24.

Bio-Imaging Unit, Newcastle University, Newcastle upon Tyne NE2 4HH, UK. Electronic address:

CD4 T cell differentiation into multiple T helper (Th) cell lineages is critical for optimal adaptive immune responses. This report identifies an intrinsic mechanism by which programmed death-1 receptor (PD-1) signaling imparted regulatory phenotype to Foxp3 Th1 cells (denoted as TbetiTreg cells) and inducible regulatory T (iTreg) cells. TbetiTreg cells prevented inflammation in murine models of experimental colitis and experimental graft versus host disease (GvHD). Read More

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http://dx.doi.org/10.1016/j.immuni.2018.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6105434PMC
August 2018
18 Reads

BST-2 controls T cell proliferation and exhaustion by shaping the early distribution of a persistent viral infection.

PLoS Pathog 2018 07 20;14(7):e1007172. Epub 2018 Jul 20.

Viral Immunology & Intravital Imaging Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, United States of America.

The interferon inducible protein, BST-2 (or, tetherin), plays an important role in the innate antiviral defense system by inhibiting the release of many enveloped viruses. Consequently, viruses have evolved strategies to counteract the anti-viral activity of this protein. While the mechanisms by which BST-2 prevents viral dissemination have been defined, less is known about how this protein shapes the early viral distribution and immunological defense against pathogens during the establishment of persistence. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6080785PMC
July 2018
2 Reads