4,004 results match your criteria Lymphocytic Choriomeningitis


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
February 2019

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

Science 2019 Feb;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 Feb 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
February 2019
1 Read

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

Immunity 2019 Jan 24. Epub 2019 Jan 24.

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
January 2019
5 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
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
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

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

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 Jan 12. Epub 2019 Jan 12.

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
January 2019

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
7 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
25 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
1 Read

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
January 2018
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 IL-10 Interferes with the Immune Response to Varicella-Zoster Virus (VZV) in Elderly Recipients of Live Attenuated Zoster Vaccine.

J Infect Dis 2018 Nov 16. Epub 2018 Nov 16.

Columbia University College of Physicians and Surgeons, Department of Pathology and Cell Biology, NY.

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

Methods: Zostavax™ was given to 26 patients (ages 60-80). Read More

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http://dx.doi.org/10.1093/infdis/jiy660DOI Listing
November 2018
10 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

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

Nat Chem Biol 2018 Dec 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
11 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
14 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
2 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
11 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
13 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

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
September 2018
7 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
6 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
7 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
3 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
23 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

Isolation and genomic characterization of lymphocytic choriomeningitis virus in ticks from northeastern China.

Transbound Emerg Dis 2018 Dec 10;65(6):1733-1739. Epub 2018 Jul 10.

School of Life Sciences and Engineering, Foshan University, Foshan, China.

Lymphocytic choriomeningitis virus (LCMV) is a rodent-borne arenavirus that is considered a neglected cause of neurologic diseases in humans. In this study, we described genomic characterization of newly isolated LCMVs in Haemaphysalis longicornis, Dermacentor nuttalli, Dermacentor silvarum and Ixodes persulcatus in Jilin Province, northeastern China. The complete sequences of the small (S) and large (L) segments of LCMVs in ticks contained 3,375 and 7,235-7,241 nucleotides, respectively. Read More

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http://dx.doi.org/10.1111/tbed.12946DOI Listing
December 2018
11 Reads

CRACR2A-Mediated TCR Signaling Promotes Local Effector Th1 and Th17 Responses.

J Immunol 2018 Aug 9;201(4):1174-1185. Epub 2018 Jul 9.

Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095;

Ca release-activated Ca channel regulator 2A (CRACR2A) is expressed abundantly in T cells and acts as a signal transmitter between TCR stimulation and activation of the Ca/NFAT and JNK/AP1 pathways. CRACR2A has been linked to human diseases in numerous genome-wide association studies and was shown to be one of the most sensitive targets of the widely used statin drugs. However, the physiological role of CRACR2A in T cell functions remains unknown. Read More

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http://dx.doi.org/10.4049/jimmunol.1800659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6081249PMC
August 2018
5 Reads

CEACAM1 promotes CD8 T cell responses and improves control of a chronic viral infection.

Nat Commun 2018 07 2;9(1):2561. Epub 2018 Jul 2.

Institute of Immunology, University Hospital Essen, Hufelandstrasse 55, 45147, Essen, Germany.

Dysfunction of CD8 T cells can lead to the development of chronic viral infection. Identifying mechanisms responsible for such T cell dysfunction is therefore of great importance to understand how to prevent persistent viral infection. Here we show using lymphocytic choriomeningitis virus (LCMV) infection that carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is fundamental for recruiting lymphocyte-specific protein kinase (Lck) into the T cell receptor complex to form an efficient immunological synapse. Read More

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http://dx.doi.org/10.1038/s41467-018-04832-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6028648PMC
July 2018
19 Reads
10.742 Impact Factor

The Kinase Complex mTOR Complex 2 Promotes the Follicular Migration and Functional Maturation of Differentiated Follicular Helper CD4 T Cells During Viral Infection.

Front Immunol 2018 23;9:1127. Epub 2018 May 23.

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

Follicular helper CD4 T (T) cells are critical for optimal B-cell-mediated humoral immunity by initiating, fueling, and sustaining germinal center reactions. The differentiation of T cells relies on multiple intrinsic and extrinsic factors; however, the details by which these factors are integrated to coordinate T differentiation are largely unknown. In this study, using a mouse model of acute lymphocytic choriomeningitis virus (LCMV) viral infection, we demonstrate that mTOR complex 2 (mTORC2) kinase integrates TCR signaling and ICOS-mediated co-stimulation to promote late differentiation and functional maturation of virus-specific T cells. Read More

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http://dx.doi.org/10.3389/fimmu.2018.01127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5974104PMC
May 2018
10 Reads

Infections: a double-edge sword in autoimmunity.

Curr Opin Rheumatol 2018 Jul;30(4):365-372

Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, affiliated to the Sackler Faculty of Medicine Tel-Aviv University.

Purpose Of Review: Infections play a role in the pathogenesis of autoimmune diseases (AID). Several bacterial and viral pathogens play a double role, as both inducers and inhibitors of AID. In this review, we will present current evidence and discuss different aspects of this notion. Read More

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http://dx.doi.org/10.1097/BOR.0000000000000490DOI Listing
July 2018
7 Reads
4.890 Impact Factor

Co-transfer of tumor-specific effector and memory CD8+ T cells enhances the efficacy of adoptive melanoma immunotherapy in a mouse model.

J Immunother Cancer 2018 May 29;6(1):41. Epub 2018 May 29.

VA Ann Arbor Healthcare System, 2215 Fuller Road, Ann Arbor, MI, 48105, USA.

Background: Adoptive cell transfer (ACT) is a promising cancer immunotherapeutic strategy that remains ineffective for a large subset of patients. ACT with memory CD8+ T cells (T) has been shown to have superior efficacy compared to traditional ACT with effector CD8+ T cells (T). T and T have complementary physiological advantages for immunotherapy, but previous publications have not examined ACT using a combination of T and T. Read More

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https://jitc.biomedcentral.com/articles/10.1186/s40425-018-0
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http://dx.doi.org/10.1186/s40425-018-0358-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5975512PMC
May 2018
19 Reads

Assessment of risk for transplant-transmissible infectious encephalitis among deceased organ donors.

Transpl Infect Dis 2018 Oct 15;20(5):e12933. Epub 2018 Jun 15.

Office of Blood, Organ, and Other Tissue Safety, Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA.

Background: There were 13 documented clusters of infectious encephalitis transmission via organ transplant from deceased donors to recipients during 2002-2013. Hence, organs from donors diagnosed with encephalitis are often declined because of concerns about the possibility of infection, given that there is no quick and simple test to detect causes of infectious encephalitis.

Methods: We constructed a database containing cases of infectious and non-infectious encephalitis. Read More

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http://dx.doi.org/10.1111/tid.12933DOI Listing
October 2018
18 Reads

Emerging Rodent-Borne Viral Zoonoses in Trento, Italy.

Ecohealth 2018 09 23;15(3):695-704. Epub 2018 May 23.

Department of Biodiversity and Molecular Ecology, Research and Innovation Center, Fondazione Edmund Mach, Via E. Mach, 1, 38010, San Michele all'Adige, TN, Italy.

Rodent-borne hanta- and arenaviruses are an emerging public health threat in Europe; however, their circulation in human populations is usually underestimated since most infections are asymptomatic. Compared to other European countries, Italy is considered 'low risk' for these viruses, yet in the Province of Trento, two pathogenic hantaviruses (Puumala and Dobrava-Belgrade virus) and one arenavirus (Lymphocytic Choriomeningitis Virus) are known to circulate in rodent reservoirs. In this paper, we performed a follow-up serological screening in humans to detect variation in the prevalence of these three viruses compared to previous analyses carried out in 2002. Read More

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http://dx.doi.org/10.1007/s10393-018-1335-4DOI Listing
September 2018
2 Reads

CD4 T Cell Affinity Diversity Is Equally Maintained during Acute and Chronic Infection.

J Immunol 2018 Jul 18;201(1):19-30. Epub 2018 May 18.

Division of Microbiology and Immunology, Department of Pathology, University of Utah, Salt Lake City, UT 84112

TCR affinity for peptide MHC dictates the functional efficiency of T cells and their propensity to differentiate into effectors and form memory. However, in the context of chronic infections, it is unclear what the overall profile of TCR affinity for Ag is and if it differs from acute infections. Using the comprehensive affinity analysis provided by the two-dimensional micropipette adhesion frequency assay and the common indirect affinity evaluation methods of MHC class II tetramer and functional avidity, we tracked IA GP-specific cells in the mouse model of acute (Armstrong) and chronic (clone 13) lymphocytic choriomeningitis virus infection. Read More

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http://dx.doi.org/10.4049/jimmunol.1800295DOI Listing

Long-Term Persistence of Exhausted CD8 T Cells in Chronic Infection Is Regulated by MicroRNA-155.

Cell Rep 2018 May;23(7):2142-2156

Department of Microbiology and Institute for Immunology, University of Pennsylvania Perelman School Medicine, Philadelphia, PA 19104, USA. Electronic address:

Persistent viral infections and tumors drive development of exhausted T (T) cells. In these settings, T cells establish an important host-pathogen or host-tumor stalemate. However, T cells erode over time, leading to loss of pathogen or cancer containment. Read More

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http://dx.doi.org/10.1016/j.celrep.2018.04.038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5986283PMC
May 2018
3 Reads

Expression of the DNA-Binding Factor TOX Promotes the Encephalitogenic Potential of Microbe-Induced Autoreactive CD8 T Cells.

Immunity 2018 05;48(5):937-950.e8

Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland; Division of Clinical Pathology, Geneva University Hospital, Geneva, Switzerland. Electronic address:

Infections are thought to trigger CD8 cytotoxic T lymphocyte (CTL) responses during autoimmunity. However, the transcriptional programs governing the tissue-destructive potential of CTLs remain poorly defined. In a model of central nervous system (CNS) inflammation, we found that infection with lymphocytic choriomeningitis virus (LCMV), but not Listeria monocytogenes (Lm), drove autoimmunity. Read More

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http://dx.doi.org/10.1016/j.immuni.2018.04.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6040915PMC
May 2018
14 Reads

Crystal structures of endonuclease domain complexed with diketo-acid ligands.

IUCrJ 2018 Mar 22;5(Pt 2):223-235. Epub 2018 Feb 22.

Aix-Marseille Université, AFMB UMR 7257, 13288 Marseille, France.

The family, together with the and families, is one of the three negative-stranded RNA viral families that encode an endonuclease in their genome. The endonuclease domain is at the N-terminus of the L protein, a multifunctional protein that includes the RNA-dependent RNA polymerase. The synthesis of mRNA in arenaviruses is a process that is primed by capped nucleotides that are 'stolen' from the cellular mRNA by the endonuclease domain in cooperation with other domains of the L protein. Read More

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http://dx.doi.org/10.1107/S2052252518001021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5947727PMC
March 2018
7 Reads

Effective Treatment of Experimental Lymphocytic Choriomeningitis Virus Infection: Consideration of Favipiravir for Use With Infected Organ Transplant Recipients.

J Infect Dis 2018 Jul;218(4):522-527

Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan.

Lymphocytic choriomeningitis virus (LCMV) poses a substantial risk to immunocompromised individuals. The case fatality rate in recent clusters of LCMV infection in immunosuppressed organ transplantation recipients has exceeded 70%. In the present study, we demonstrate potent antiviral activity of favipiravir against acute, disseminated LCMV infection in NZB mice. Read More

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http://dx.doi.org/10.1093/infdis/jiy159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6047442PMC
July 2018
4 Reads

The thioredoxin-1 system is essential for fueling DNA synthesis during T-cell metabolic reprogramming and proliferation.

Nat Commun 2018 05 10;9(1):1851. Epub 2018 May 10.

Institute of Molecular Health Sciences, ETH Zurich, 8093, Zürich, Switzerland.

The thioredoxin-1 (Trx1) system is an important contributor to cellular redox balance and is a sensor of energy and glucose metabolism. Here we show critical c-Myc-dependent activation of the Trx1 system during thymocyte and peripheral T-cell proliferation, but repression during T-cell quiescence. Deletion of thioredoxin reductase-1 (Txnrd1) prevents expansion the CD4CD8 thymocyte population, whereas Txnrd1 deletion in CD4CD8 thymocytes does not affect further maturation and peripheral homeostasis of αβT cells. Read More

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http://dx.doi.org/10.1038/s41467-018-04274-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5945637PMC
May 2018
8 Reads

The adaptor molecule CD2AP in CD4 T cells modulates differentiation of follicular helper T cells during chronic LCMV infection.

PLoS Pathog 2018 05 7;14(5):e1007053. Epub 2018 May 7.

Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri, United States of America.

CD4 T cell-mediated help to CD8 T cells and B cells is a critical arm of the adaptive immune system required for control of pathogen infection. CD4 T cells express cytokines and co-stimulatory molecules that support a sustained CD8 T cell response and also enhance generation of protective antibody by germinal center B cells. However, the molecular components that modulate CD4 T cell functions in response to viral infection or vaccine are incompletely understood. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5957453PMC
May 2018
4 Reads

C1q restrains autoimmunity and viral infection by regulating CD8 T cell metabolism.

Science 2018 05;360(6388):558-563

Faculty of Medicine, Imperial College London, London W12 ONN, UK.

Deficiency of C1q, the initiator of the complement classical pathway, is associated with the development of systemic lupus erythematosus (SLE). Explaining this association in terms of abnormalities in the classical pathway alone remains problematic because C3 deficiency does not predispose to SLE. Here, using a mouse model of SLE, we demonstrate that C1q, but not C3, restrains the response to self-antigens by modulating the mitochondrial metabolism of CD8 T cells, which can themselves propagate autoimmunity. Read More

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http://dx.doi.org/10.1126/science.aao4555DOI Listing
May 2018
7 Reads