3,963 results match your criteria Lymphocytic Choriomeningitis


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

Transbound Emerg Dis 2018 Jul 10. 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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July 2018
2 Reads

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

J Immunol 2018 Jul 9. 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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July 2018
1 Read

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

Nat Commun 2018 Jul 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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July 2018
6 Reads

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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May 2018
2 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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July 2018
1 Read

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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May 2018
1 Read

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

Transpl Infect Dis 2018 May 29:e12933. Epub 2018 May 29.

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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May 2018
2 Reads

Emerging Rodent-Borne Viral Zoonoses in Trento, Italy.

Ecohealth 2018 May 23. 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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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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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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Expression of the DNA-Binding Factor TOX Promotes the Encephalitogenic Potential of Microbe-Induced Autoreactive CD8 T Cells.

Immunity 2018 May;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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May 2018
6 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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March 2018
5 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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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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Weak vaccinia virus-induced NK cell regulation of CD4 T cells is associated with reduced NK cell differentiation and cytolytic activity.

Virology 2018 06 30;519:131-144. Epub 2018 Apr 30.

Department of Pathology, University of Massachusetts Medical School, 368 Plantation Street, ASC9-2014E, Worcester, MA 01605, USA. Electronic address:

Natural killer (NK) cells control antiviral adaptive immune responses in mice during some virus infections, but the universality of this phenomenon remains unknown. Lymphocytic choriomeningitis virus (LCMV) infection of mice triggered potent cytotoxic activity of NK cells (NK) against activated CD4 T cells, tumor cells, and allogeneic lymphocytes. In contrast, NK cells activated by vaccinia virus (VACV) infection (NK) exhibited weaker cytolytic activity against each of these target cells. Read More

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June 2018
3 Reads

Oncolytic activity of the rhabdovirus VSV-GP against prostate cancer.

Int J Cancer 2018 Apr 26. Epub 2018 Apr 26.

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

Oncolytic viruses, including the oncolytic rhabdovirus VSV-GP tested here, selectively infect and kill cancer cells and are a promising new therapeutic modality. Our aim was to study the efficacy of VSV-GP, a vesicular stomatitis virus carrying the glycoprotein of lymphocytic choriomeningitis virus, against prostate cancer, for which current treatment options still fail to cure metastatic disease. VSV-GP was found to infect 6 of 7 prostate cancer cell lines with great efficacy. Read More

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April 2018
1 Read

Deletion of Inflammasome Components Is Not Sufficient To Prevent Fatal Inflammation in Models of Familial Hemophagocytic Lymphohistiocytosis.

J Immunol 2018 Jun 25;200(11):3769-3776. Epub 2018 Apr 25.

Centre International de Recherche en Infectiologie, Lyon 69007, France;

Hemophagocytic lymphohistiocytosis (HLH) is a severe inflammatory condition that occurs in patients with genetic defects of cytotoxicity (familial HLH [FHL]) or secondary to other immunological disorders such as juvenile idiopathic arthritis. HLH is characterized by elevated levels of serum IL-18 and other cytokines. Moreover, a novel clinical entity has been recently identified in which constitutive NLRC4 inflammasome activation leads to severe HLH. Read More

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Tr1 cell immunotherapy promotes transplant tolerance via de novo Tr1 cell induction in mice and is safe and effective during acute viral infection.

Eur J Immunol 2018 Apr 23. Epub 2018 Apr 23.

Division of Immunology Transplantation and Infectious Diseases (DITID), Diabetes Research Institute (DRI) IRCCS San Raffaele Scientific Institute, Milan, Italy.

Tr1 cell therapy is considered an emerging approach to improve transplant tolerance and enhance allogeneic graft survival. However, it remains unclear how Tr1 cells promote transplant tolerance and whether they will be safe and stable in the face of an acute viral infection. By employing a mouse model of pancreatic islet transplantation, we report that Tr1 cell therapy promoted transplant tolerance via de novo induction of Tr1 cells in the recipients. Read More

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April 2018
1 Read

Viral Diversity of House Mice in New York City.

MBio 2018 Apr 17;9(2). Epub 2018 Apr 17.

Center for Infection and Immunity, Columbia University, New York, New York, USA

The microbiome of wild (house mouse), a globally distributed invasive pest that resides in close contact with humans in urban centers, is largely unexplored. Here, we report analysis of the fecal virome of house mice in residential buildings in New York City, NY. Mice were collected at seven sites in Manhattan, Queens, Brooklyn, and the Bronx over a period of 1 year. Read More

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A flexible MHC class I multimer loading system for large-scale detection of antigen-specific T cells.

J Exp Med 2018 May 17;215(5):1493-1504. Epub 2018 Apr 17.

Oncode Institute and Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, Netherlands

Adaptive immunity is initiated by T cell recognition of specific antigens presented by major histocompatibility complexes (MHCs). MHC multimer technology has been developed for the detection, isolation, and characterization of T cells in infection, autoimmunity, and cancer. Here, we present a simple, fast, flexible, and efficient method to generate many different MHC class I (MHC I) multimers in parallel using temperature-mediated peptide exchange. Read More

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Replication-incompetent rabies virus vector harboring glycoprotein gene of lymphocytic choriomeningitis virus (LCMV) protects mice from LCMV challenge.

PLoS Negl Trop Dis 2018 04 16;12(4):e0006398. Epub 2018 Apr 16.

Department of virology I, National Institute of Infectious Diseases, Toyama, Shinjuku-ku, Tokyo, Japan.

Background: Lymphocytic choriomeningitis virus (LCMV) causes a variety of diseases, including asymptomatic infections, meningitis, and congenital infections in the fetus of infected mother. The development of a safe and effective vaccine against LCMV is imperative. This study aims to develop a new candidate vaccine against LCMV using a recombinant replication-incompetent rabies virus (RV) vector. Read More

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April 2018
2 Reads

Role of PD-1 during effector CD8 T cell differentiation.

Proc Natl Acad Sci U S A 2018 May 13;115(18):4749-4754. Epub 2018 Apr 13.

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

PD-1 (programmed cell death-1) is the central inhibitory receptor regulating CD8 T cell exhaustion during chronic viral infection and cancer. Interestingly, PD-1 is also expressed transiently by activated CD8 T cells during acute viral infection, but the role of PD-1 in modulating T cell effector differentiation and function is not well defined. To address this question, we examined the expression kinetics and role of PD-1 during acute lymphocytic choriomeningitis virus (LCMV) infection of mice. Read More

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May 2018
1 Read

Visualization of Arenavirus RNA Species in Individual Cells by Single-Molecule Fluorescence Hybridization Suggests a Model of Cyclical Infection and Clearance during Persistence.

J Virol 2018 06 29;92(12). Epub 2018 May 29.

Department of Medicine, Division of Immunobiology, University of Vermont, Burlington, Vermont, USA

Lymphocytic choriomeningitis mammarenavirus (LCMV) is an enveloped, negative-strand RNA virus that causes serious disease in humans but establishes an asymptomatic, lifelong infection in reservoir rodents. Different models have been proposed to describe how arenaviruses regulate the replication and transcription of their bisegmented, single-stranded RNA genomes, particularly during persistent infection. However, these models were based largely on viral RNA profiling data derived from entire populations of cells. Read More

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June 2018
9 Reads

Individually addressable and dynamic DNA gates for multiplexed cell sorting.

Proc Natl Acad Sci U S A 2018 Apr 9;115(17):4357-4362. Epub 2018 Apr 9.

Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA 30332;

The ability to analyze and isolate cells based on the expression of specific surface markers has increased our understanding of cell biology and produced numerous applications for biomedicine. However, established cell-sorting platforms rely on labels that are limited in number due to biophysical constraints, such as overlapping emission spectra of fluorophores in FACS. Here, we establish a framework built on a system of orthogonal and extensible DNA gates for multiplexed cell sorting. Read More

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April 2018
1 Read

Dynamics of Lymphocyte Reconstitution After Hematopoietic Transplantation During Chronic Lymphocytic Choriomeningitis Virus Infection.

AIDS Res Hum Retroviruses 2018 May 18;34(5):430-438. Epub 2018 Apr 18.

Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University , Chicago, Illinois.

Bone marrow transplantation is a treatment for various cancers and genetic diseases, and the only case of a cured HIV infection involved the use of this clinical procedure, highlighting the potential use of this therapy for curing many chronic diseases. However, little is known about how chronic viral infection influences lymphocyte reconstitution after bone marrow transplantation. To address this, we infected mice with chronic lymphocytic choriomeningitis virus, and performed bone marrow transplantation to assess lymphocyte reconstitution. Read More

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May 2018
5 Reads

Lymphocytic choriomeningitis virus infection of dendritic cells interferes with TLR-induced IL-12/IL-23 cytokine production in an IL-10 independent manner.

Cytokine 2018 Aug 27;108:105-114. Epub 2018 Mar 27.

Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Canada. Electronic address:

Dendritic cells produce IL-12 and IL-23 in response to viral and bacterial infection and these cytokines are responsible for successful pathogen clearance. How sequential viral and bacterial infections affect the production of IL-12 and IL-23 is currently not known. Our study demonstrates that in dendritic cells infected with Lymphocytic choriomeningitis virus (LCMV), TLR activation with bacterial PAMPs resulted in reduced IL-12 and IL-23 expression compared to non-infected cells. Read More

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August 2018
1 Read

Interleukin-27R Signaling Mediates Early Viral Containment and Impacts Innate and Adaptive Immunity after Chronic Lymphocytic Choriomeningitis Virus Infection.

J Virol 2018 06 29;92(12). Epub 2018 May 29.

Molecular Biology Section, Division of Biological Sciences, University of California San Diego, La Jolla, California, USA

Chronic viral infections represent a major challenge to the host immune response, and a unique network of immunological elements, including cytokines, are required for their containment. By using a model persistent infection with the natural murine pathogen lymphocytic choriomeningitis virus clone 13 (LCMV Cl13) we investigated the role of one such cytokine, interleukin-27 (IL-27), in the control of chronic infection. We found that IL-27 receptor (IL-27R) signaling promoted control of LCMV Cl13 as early as days 1 and 5 after infection and that transcripts were rapidly elevated in multiple subsets of dendritic cells (DCs) and myeloid cells. Read More

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June 2018
1 Read

A Highly Conserved Leucine in Mammarenavirus Matrix Z Protein Is Required for Z Interaction with the Virus L Polymerase and Z Stability in Cells Harboring an Active Viral Ribonucleoprotein.

J Virol 2018 06 14;92(11). Epub 2018 May 14.

Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, USA

Mammarenaviruses cause chronic infections in their natural rodent hosts. Infected rodents shed infectious virus into excreta. Humans are infected through mucosal exposure to aerosols or direct contact of abraded skin with fomites, resulting in a wide range of manifestations from asymptomatic or mild febrile illness to severe life-threatening hemorrhagic fever. Read More

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Hypoxic marker CA IX and adhesion mediator β-catenin are downregulated by lymphocytic choriomeningitis virus persistent infection.

Oncotarget 2018 Feb 2;9(16):12879-12893. Epub 2018 Feb 2.

Institute of Virology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava 845 05, Slovak Republic.

Renal cell carcinoma is one of the most frequent cancer diseases with high resistance to radio- and chemotherapy. Mutation of VHL gene is frequent in these tumors leading to simulation of hypoxic conditions. Lymphocytic choriomeningitis virus, belonging to RNA viruses, is a neglected human pathogen and teratogen. Read More

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February 2018

Adenovirus Vector Vaccination Impacts NK Cell Rheostat Function following Lymphocytic Choriomeningitis Virus Infection.

J Virol 2018 06 14;92(11). Epub 2018 May 14.

Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA

Natural killer (NK) cells respond rapidly as a first line of defense against infectious pathogens. In addition, NK cells may provide a "rheostat" function and have been shown to reduce the magnitude of antigen-specific T cell responses following infection to avoid immunopathology. However, it remains unknown whether NK cells similarly modulate vaccine-elicited T cell responses following virus challenge. Read More

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Tim-3 co-stimulation promotes short-lived effector T cells, restricts memory precursors, and is dispensable for T cell exhaustion.

Proc Natl Acad Sci U S A 2018 Mar 20;115(10):2455-2460. Epub 2018 Feb 20.

Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261;

Tim-3 is highly expressed on a subset of T cells during T cell exhaustion in settings of chronic viral infection and tumors. Using lymphocytic choriomeningitis virus (LCMV) Clone 13, a model for chronic infection, we found that Tim-3 was neither necessary nor sufficient for the development of T cell exhaustion. Nonetheless, expression of Tim-3 was sufficient to drive resistance to PD-L1 blockade therapy during chronic infection. Read More

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March 2018
1 Read

Interactome analysis of the lymphocytic choriomeningitis virus nucleoprotein in infected cells reveals ATPase Na+/K+ transporting subunit Alpha 1 and prohibitin as host-cell factors involved in the life cycle of mammarenaviruses.

PLoS Pathog 2018 02 20;14(2):e1006892. Epub 2018 Feb 20.

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

Several mammalian arenaviruses (mammarenaviruses) cause hemorrhagic fevers in humans and pose serious public health concerns in their endemic regions. Additionally, mounting evidence indicates that the worldwide-distributed, prototypic mammarenavirus, lymphocytic choriomeningitis virus (LCMV), is a neglected human pathogen of clinical significance. Concerns about human-pathogenic mammarenaviruses are exacerbated by of the lack of licensed vaccines, and current anti-mammarenavirus therapy is limited to off-label use of ribavirin that is only partially effective. Read More

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February 2018

B cells are the predominant mediators of early systemic viral dissemination during rectal LCMV infection.

Mucosal Immunol 2018 Jul 19;11(4):1158-1167. Epub 2018 Feb 19.

Virology and Immunology, Gladstone Institutes, San Francisco, CA, 94158, USA.

Determining the magnitude of local immune response during mucosal exposure to viral pathogens is critical to understanding the mechanism of viral pathogenesis. We previously showed that vaginal inoculation of lymphocytic choriomeningitis virus (LCMV) fails to induce a robust innate immune response in the lower female reproductive tract (FRT), allowing high titer viral replication and a delay in T-cell-mediated viral control. Despite this immunological delay, LCMV replication remained confined mainly to the FRT and the draining iliac lymph node. Read More

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July 2018
1 Read

Mammarenaviruses deleted from their Z gene are replicative and produce an infectious progeny in BHK-21 cells.

Virology 2018 05 16;518:34-44. Epub 2018 Feb 16.

Unité de virologie, Département de Biologie des Agents Transmissibles, Institut de Recherche Biomédicale des Armées, 1 place général Valérie André, BP 73 91 223 Brétigny-sur-Orge cedex, France. Electronic address:

Mammarenaviruses bud out of infected cells via the recruitment of the endosomal sorting complex required for transport through late domain motifs localized into their Z protein. Here, we demonstrated that mammarenaviruses lacking this protein can be rescued and are replicative, despite a 3-log reduction in virion production, in BHK-21 cells, but not in five other cell lines. Mutations of putative late domain motifs identified into the viral nucleoprotein resulted in the almost complete abolition of infectious virion production by Z-deleted mammarenaviruses. Read More

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May 2018
1 Read

Sustained Id2 regulation of E proteins is required for terminal differentiation of effector CD8 T cells.

J Exp Med 2018 Mar 12;215(3):773-783. Epub 2018 Feb 12.

Department of Biological Sciences, University of California, San Diego, La Jolla, CA

CD8 T cells responding to infection differentiate into a heterogeneous population composed of progeny that are short-lived and participate in the immediate, acute response and those that provide long-lasting host protection. Although it is appreciated that distinct functional and phenotypic CD8 T cell subsets persist, it is unclear whether there is plasticity among subsets and what mechanisms maintain subset-specific differences. Here, we show that continued Id2 regulation of E-protein activity is required to maintain the KLRG1 CD8 T cell population after lymphocytic choriomeningitis virus infection. Read More

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March 2018
1 Read

Mammarenaviral Infection Is Dependent on Directional Exposure to and Release from Polarized Intestinal Epithelia.

Viruses 2018 02 10;10(2). Epub 2018 Feb 10.

Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, Louisville, KY 40202, USA.

Mammarenavirusesare single-stranded RNA viruses with a bisegmented ambisense genome. Ingestion has been shown as a natural route of transmission for both Lassa virus (LASV) and Lymphocytic choriomeningitis virus (LCMV). Due to the mechanism of transmission, epithelial tissues are among the first host cells to come in contact with the viruses, and as such they potentially play a role in spread of virus to naïve hosts. Read More

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February 2018
4 Reads

IFN-Gamma-Dependent and Independent Mechanisms of CD4⁺ Memory T Cell-Mediated Protection from Listeria Infection.

Pathogens 2018 Feb 13;7(1). Epub 2018 Feb 13.

Department of Pathology, University of Utah, Salt Lake City, UT 84112, USA.

While CD8⁺ memory T cells can promote long-lived protection from secondary exposure to intracellular pathogens, less is known regarding the direct protective mechanisms of CD4⁺ T cells. We utilized a prime/boost model in which mice are initially exposed to an acutely infecting strain of lymphocytic choriomeningitis virus (LCMV), followed by a heterologous rechallenge with recombinantly expressing the MHC Class II-restricted LCMV epitope, GP (Lm-gp61). We found that heterologous Lm-gp61 rechallenge resulted in robust activation of CD4⁺ memory T cells and that they were required for rapid bacterial clearance. Read More

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February 2018

Many Th Cell Subsets Have Fas Ligand-Dependent Cytotoxic Potential.

J Immunol 2018 Mar 7;200(6):2004-2012. Epub 2018 Feb 7.

Department of Microbiology and Immunology, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455

CD4 Th cells can have cytotoxic activity against cells displaying relevant peptide-MHC class II (p:MHCII) ligands. Cytotoxicity may be a property of Th1 cells and depends on perforin and the Eomes transcription factor. We assessed these assertions for polyclonal p:MHCII-specific CD4 T cells activated in vivo in different contexts. Read More

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Mining a Kröhnke Pyridine Library for Anti-Arenavirus Activity.

ACS Infect Dis 2018 May 1;4(5):815-824. Epub 2018 Mar 1.

Several arenaviruses cause hemorrhagic fever (HF) disease in humans and represent important public health problems in their endemic regions. In addition, evidence indicates that the worldwide-distributed prototypic arenavirus lymphocytic choriomeningitis virus is a neglected human pathogen of clinical significance. There are no licensed arenavirus vaccines, and current antiarenavirus therapy is limited to an off-label use of ribavirin that is only partially effective. Read More

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IL-33 induces immunosuppressive neutrophils via a type 2 innate lymphoid cell/IL-13/STAT6 axis and protects the liver against injury in LCMV infection-induced viral hepatitis.

Cell Mol Immunol 2018 Feb 5. Epub 2018 Feb 5.

Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555-1070, USA.

Viral hepatitis is still a public health problem affecting several million people around the world. Neutrophils are polymorphonuclear cells that have a critical role in antibacterial infection. However, the role of neutrophils in viral infection is not fully understood. Read More

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February 2018
10 Reads

The use of novel epitope-tagged arenaviruses reveals that Rab5c-positive endosomal membranes are targeted by the LCMV matrix protein.

J Gen Virol 2018 Feb;99(2):187-193

3​Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USA.

We report the development of recombinant New World (Junín; JUNV) and Old World (lymphocytic choriomeningitis virus; LCMV) mammarenaviruses that encode an HA-tagged matrix protein (Z). These viruses permit the robust affinity purification of Z from infected cells or virions, as well as the detection of Z by immunofluorescent microscopy. Importantly, the HA-tagged viruses grow with wild-type kinetics in a multi-cycle growth assay. Read More

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February 2018
3 Reads

Analyzing Mouse B Cell Responses Specific to LCMV Infection.

Methods Mol Biol 2018 ;1707:15-38

Institute of Immunology, Third Military Medical University, Gaotanyan, Shapingba District, Chongqing, 400038, China.

B cell responses play a central role in humoral immunity, which protects an individual from invading pathogens by antigen-specific antibodies. Understanding the basic principles of the B cell responses during viral infection is of substantial importance for anti-viral vaccine development. In inbred mice, lymphocytic choriomeningitis virus (LCMV) infection elicits robust and typical T cell-dependent B cell responses, including germinal center reaction, memory B cell formation, and a long-lived plasma cell pool in bone marrow. Read More

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January 2018
6 Reads

Locus-Specific Reversible DNA Methylation Regulates Transient IL-10 Expression in Th1 Cells.

J Immunol 2018 Mar 26;200(5):1865-1875. Epub 2018 Jan 26.

Academy of Immunology and Microbiology, Institute for Basic Science, Pohang 37673, Republic of Korea;

IL-10 is a pleiotropic cytokine with multifaceted functions in establishing immune homeostasis. Although expressed by Th1 and Th2 cells, conventional Th1 cells produce marginal levels of IL-10 compared with their Th2 counterparts. In this study, we investigated the epigenetic mechanisms of gene expression in Th1 cells. Read More

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The Contribution of Cytomegalovirus Infection to Immune Senescence Is Set by the Infectious Dose.

Front Immunol 2017 10;8:1953. Epub 2018 Jan 10.

Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands.

The relationship between human cytomegalovirus (HCMV) infections and accelerated immune senescence is controversial. Whereas some studies reported a CMV-associated impaired capacity to control heterologous infections at old age, other studies could not confirm this. We hypothesized that these discrepancies might relate to the variability in the infectious dose of CMV occurring in real life. Read More

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January 2018
3 Reads

T-cell gene therapy for perforin deficiency corrects cytotoxicity defects and prevents hemophagocytic lymphohistiocytosis manifestations.

J Allergy Clin Immunol 2018 Jan 31. Epub 2018 Jan 31.

Infection, Immunity, Inflammation, Molecular and Cellular Immunology Section, UCL Great Ormond Street Institute of Child Health, London, United Kingdom. Electronic address:

Background: Mutations in the perforin 1 (PRF1) gene account for up to 58% of familial hemophagocytic lymphohistiocytosis syndromes. The resulting defects in effector cell cytotoxicity lead to hypercytokinemia and hyperactivation with inflammation in various organs.

Objective: We sought to determine whether autologous gene-corrected T cells can restore cytotoxic function, reduce disease activity, and prevent hemophagocytic lymphohistiocytosis (HLH) symptoms in in vivo models. Read More

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January 2018
4 Reads

Efficacy of a Virus-Like Nanoparticle As Treatment for a Chronic Viral Infection Is Hindered by IRAK1 Regulation and Antibody Interference.

Front Immunol 2017 4;8:1885. Epub 2018 Jan 4.

Immunovirology Laboratory, Institut national de la recherche scientifique (INRS), INRS-Institut Armand-Frappier, Laval, Quebec, Canada.

Although vaccination has been an effective way of preventing infections ever since the eighteenth century, the generation of therapeutic vaccines and immunotherapies is still a work in progress. A number of challenges impede the development of these therapeutic approaches such as safety issues related to the administration of whole pathogens whether attenuated or inactivated. One safe alternative to classical vaccination methods gaining recognition is the use of nanoparticles, whether synthetic or naturally derived. Read More

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January 2018
6 Reads

Inhibition of the Fibrinogen-Like Protein 2:FcγRIIB/RIII immunosuppressive pathway enhances antiviral T-cell and B-cell responses leading to clearance of lymphocytic choriomeningitis virus clone 13.

Immunology 2018 Jul 20;154(3):476-489. Epub 2018 Feb 20.

Toronto General Hospital, Multi Organ Transplant Programme, Toronto, ON, Canada.

Persistent viruses evade immune detection by interfering with virus-specific innate and adaptive antiviral immune responses. Fibrinogen-like protein-2 (FGL2) is a potent effector molecule of CD4  CD25  FoxP3 regulatory T cells and exerts its immunosuppressive activity following ligation to its cognate receptor, FcγRIIB/RIII. The role of FGL2 in the pathogenesis of chronic viral infection caused by lymphocytic choriomeningitis virus clone-13 (LCMV cl-13) was assessed in this study. Read More

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July 2018
14 Reads

Modeling tumor immunity of mouse glioblastoma by exhausted CD8 T cells.

Sci Rep 2018 Jan 9;8(1):208. Epub 2018 Jan 9.

Harvey W. Cushing Neuro-oncology Laboratories (HCNL), Department of Neurosurgery, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, 02115, USA.

T cell exhaustion occurs during chronic infection and cancers. Programmed cell death protein-1 (PD-1) is a major inhibitory checkpoint receptor involved in T cell exhaustion. Blocking antibodies (Abs) against PD-1 or its ligand, PD-L1, have been shown to reverse T cell exhaustion during chronic infection and cancers, leading to improved control of persistent antigen. Read More

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January 2018
17 Reads

Acute stimulation generates Tim-3-expressing T helper type 1 CD4 T cells that persist in vivo and show enhanced effector function.

Immunology 2018 Jul 8;154(3):418-433. Epub 2018 Feb 8.

Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA, USA.

T-cell immunoglobulin and mucin domain 3 (Tim-3) is a surface receptor expressed by T helper type 1 (Th1) effector CD4 T cells, which are critical for defence against intracellular pathogens and have been implicated in autoimmune disease. Previous studies showed that Tim-3 expression makes Th1 cells more susceptible to apoptosis and also marks functionally impaired T cells that arise due to chronic stimulation. However, other studies suggested that Tim-3-expressing Th1 cells do not always have these properties. Read More

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The Effects of Dendritic Cell Hypersensitivity on Persistent Viral Infection.

J Immunol 2018 Feb 8;200(4):1335-1346. Epub 2018 Jan 8.

Division of Biological Sciences, Molecular Biology Section, University of California, San Diego, La Jolla, CA 92093; and

Caspase-8 (CASP8) is known as an executioner of apoptosis, but more recent studies have shown that it participates in the regulation of necroptosis and innate immunity. In this study, we show that CASP8 negatively regulates retinoic acid-inducible gene I (RIG-I) signaling such that, in its absence, stimulation of the RIG-I pathway in dendritic cells (DCs) produced modestly enhanced activation of IFN regulatory factor 3 with correspondingly greater amounts of proinflammatory cytokines. In addition, mice lacking DC-specific CASP8 ( mice) develop age-dependent symptoms of autoimmune disease characterized by hyperactive DCs and T cells, spleen and liver immunopathology, and the appearance of Th1-polarized CD4 T cells. Read More

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February 2018
2 Reads