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    3941 results match your criteria Lymphocytic Choriomeningitis

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    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

    A flexible MHC class I multimer loading system for large-scale detection of antigen-specific T cells.
    J Exp Med 2018 Apr 17. 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

    Replication-incompetent rabies virus vector harboring glycoprotein gene of lymphocytic choriomeningitis virus (LCMV) protects mice from LCMV challenge.
    PLoS Negl Trop Dis 2018 Apr 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

    Role of PD-1 during effector CD8 T cell differentiation.
    Proc Natl Acad Sci U S A 2018 Apr 13. 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

    Visualization of arenavirus RNA species in individual cells by single-molecule fluorescence in situ hybridization (smFISH) suggests a model of cyclical infection and clearance during persistence.
    J Virol 2018 Apr 11. Epub 2018 Apr 11.
    Department of Medicine, Division of Immunobiology, University of Vermont, Burlington, VT 05405, USA
    Lymphocytic choriomeningitis mammarenvirus (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 largely based on viral RNA profiling data derived from entire populations of cells. Read More

    Individually addressable and dynamic DNA gates for multiplexed cell sorting.
    Proc Natl Acad Sci U S A 2018 Apr 9. 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

    Dynamics of Lymphocyte Reconstitution After Hematopoietic Transplantation During Chronic Lymphocytic Choriomeningitis Virus Infection.
    AIDS Res Hum Retroviruses 2018 Apr 18. 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

    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 Mar 26;108:105-114. Epub 2018 Mar 26.
    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

    IL-27R signalling mediates early viral containment and impacts innate and adaptive immunity after chronic lymphocytic choriomeningitis virus infection.
    J Virol 2018 Mar 28. Epub 2018 Mar 28.
    Molecular Biology Section, Division of Biological Sciences, University of California San Diego, La Jolla, CA. 92093
    Chronic viral infections represent a major challenge to host's 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-27R signalling promoted control of LCMV Cl13 as early as day 1 and 5 after infection and that transcripts were rapidly elevated in multiple subsets of dendritic cells (DCs) and myeloid cells. Read More

    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 Mar 28. Epub 2018 Mar 28.
    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

    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

    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

    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 Feb 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

    B cells are the predominant mediators of early systemic viral dissemination during rectal LCMV infection.
    Mucosal Immunol 2018 Feb 19. 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

    Mammarenaviruses deleted from their Z gene are replicative and produce an infectious progeny in BHK-21 cells.
    Virology 2018 Feb 13;518:34-44. Epub 2018 Feb 13.
    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

    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

    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

    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

    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

    Mining a Kröhnke Pyridine Library for Anti-Arenavirus Activity.
    ACS Infect Dis 2018 Mar 1. Epub 2018 Mar 1.
    Departments of Chemistry, Immunology and Microbiology, The Skaggs Institute for Chemical Biology, The WIRM Institute and §Department of Immunology and Microbiology, The Scripps Research Institute , 10550 N. Torrey Pines Road, IMM-6, La Jolla, California 92037, United States.
    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

    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

    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

    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

    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

    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

    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

    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

    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 Jan 17. Epub 2018 Jan 17.
    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

    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

    Acute stimulation generates Tim-3-expressing T helper type 1 CD4 T cells that persist in vivo and show enhanced effector function.
    Immunology 2018 Jan 9. Epub 2018 Jan 9.
    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

    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

    Sustained IFN-I Expression during Established Persistent Viral Infection: A "Bad Seed" for Protective Immunity.
    Viruses 2017 12 30;10(1). Epub 2017 Dec 30.
    Institut National de la Recherche Scientifique (INRS)-Institut Armand-Frappier, 531 Boulevard des Prairies, Laval, H7V 1B7 QC, Canada.
    Type I interferons (IFN-I) are one of the primary immune defenses against viruses. Similar to all other molecular mechanisms that are central to eliciting protective immune responses, IFN-I expression is subject to homeostatic controls that regulate cytokine levels upon clearing the infection. However, in the case of established persistent viral infection, sustained elevation of IFN-I expression bears deleterious effects to the host and is today considered as the major driver of inflammation and immunosuppression. Read More

    Gene transfer into hematopoietic stem cells reduces HLH manifestations in a murine model of Munc13-4 deficiency.
    Blood Adv 2017 Dec 21;1(27):2781-2789. Epub 2017 Dec 21.
    Human Lymphohaematopoiesis Laboratory, INSERM U1163, Paris, France.
    Patients with mutations in the gene (coding for Munc13-4 protein) suffer from familial hemophagocytic lymphohistiocytosis type 3 (FHL3), a life-threatening immune and hyperinflammatory disorder. The only curative treatment is allogeneic hematopoietic stem cell (HSC) transplantation, although the posttreatment survival rate is not satisfactory. Here, we demonstrate the curative potential of gene correction of HSCs in a murine model of FHL3. Read More

    Lamp1 Increases the Efficiency of Lassa Virus Infection by Promoting Fusion in Less Acidic Endosomal Compartments.
    MBio 2018 Jan 2;9(1). Epub 2018 Jan 2.
    Department of Microbiology, University of Virginia, Charlottesville, Virginia, USA
    Lassa virus (LASV) is an arenavirus whose entry into host cells is mediated by a glycoprotein complex (GPC) comprised of a receptor binding subunit, GP1, a fusogenic transmembrane subunit, GP2, and a stable signal peptide. After receptor-mediated internalization, arenaviruses converge in the endocytic pathway, where they are thought to undergo low-pH-triggered, GPC-mediated fusion with a late endosome membrane. A unique feature of LASV entry is a pH-dependent switch from a primary cell surface receptor (α-dystroglycan) to an endosomal receptor, lysosomal-associated membrane protein (Lamp1). Read More

    Congenital lymphocytic choriomeningitis virus-an underdiagnosed fetal teratogen.
    J AAPOS 2018 Feb 20;22(1):79-81.e1. Epub 2017 Dec 20.
    Northwestern University Feinberg School of Medicine and the Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois. Electronic address:
    Congenital lymphocytic choriomeningitis virus (LCMV) infection is associated with high mortality and morbidity. Although the number of cases reported in the literature has been increasing, it might still be clinically an underdiagnosed human fetal teratogen. We report 2 more cases of serologically proven congenital LCMV infection. Read More

    Characterization of host proteins interacting with the lymphocytic choriomeningitis virus L protein.
    PLoS Pathog 2017 Dec 20;13(12):e1006758. Epub 2017 Dec 20.
    CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse, Vienna, Austria.
    RNA-dependent RNA polymerases (RdRps) play a key role in the life cycle of RNA viruses and impact their immunobiology. The arenavirus lymphocytic choriomeningitis virus (LCMV) strain Clone 13 provides a benchmark model for studying chronic infection. A major genetic determinant for its ability to persist maps to a single amino acid exchange in the viral L protein, which exhibits RdRp activity, yet its functional consequences remain elusive. Read More

    Crystal structures of H-2Db in complex with the LCMV-derived peptides GP92 and GP392 explain pleiotropic effects of glycosylation on antigen presentation and immunogenicity.
    PLoS One 2017 18;12(12):e0189584. Epub 2017 Dec 18.
    Science for Life Laboratory, Department of Medicine Solna, Karolinska Institutet, and Department of Infectious Diseases, Karolinska University Hospital, Solna, Stockholm, Sweden.
    Post-translational modifications significantly broaden the epitope repertoire for major histocompatibility class I complexes (MHC-I) and may allow viruses to escape immune recognition. Lymphocytic choriomeningitis virus (LCMV) infection of H-2b mice generates CD8+ CTL responses directed towards several MHC-I-restricted epitopes including the peptides GP92 (CSANNSHHYI) and GP392 (WLVTNGSYL), both with a N-glycosylation site. Interestingly, glycosylation has different effects on the immunogenicity and association capacity of these two epitopes to H-2Db. Read More

    M(IL-4) Tissue Macrophages Support Efficient Interferon-Gamma Production in Antigen-Specific CD8 T Cells with Reduced Proliferative Capacity.
    Front Immunol 2017 30;8:1629. Epub 2017 Nov 30.
    Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
    CD8 cytotoxic T cell (CTL) responses are necessary for the lysis of virally infected cells and control of infection. CTLs are activated when their TCRs bind a major histocompatibility complex (MHC)-I/peptide complex on the surface of antigen presenting cells such as macrophages (MΦ). It is now apparent that MΦ display remarkable plasticity in response to environmental signals to polarize into classically activated M(LPS + IFN-γ) or alternatively activated M(IL-4). Read More

    Transcription Factor IRF4 Promotes CD8 T Cell Exhaustion and Limits the Development of Memory-like T Cells during Chronic Infection.
    Immunity 2017 12 12;47(6):1129-1141.e5. Epub 2017 Dec 12.
    The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia; Department of Microbiology and Immunology, The University of Melbourne, Parkville, VIC 3010, Australia; The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia. Electronic address:
    During chronic stimulation, CD8 T cells acquire an exhausted phenotype characterized by expression of inhibitory receptors, down-modulation of effector function, and metabolic impairments. T cell exhaustion protects from excessive immunopathology but limits clearance of virus-infected or tumor cells. We transcriptionally profiled antigen-specific T cells from mice infected with lymphocytic choriomeningitis virus strains that cause acute or chronic disease. Read More

    Axl Can Serve as Entry Factor for Lassa Virus Depending on the Functional Glycosylation of Dystroglycan.
    J Virol 2018 03 12;92(5). Epub 2018 Feb 12.
    Institute of Microbiology, Lausanne University Hospital, Lausanne, Switzerland
    Fatal infection with the highly pathogenic Lassa virus (LASV) is characterized by extensive viral dissemination, indicating broad tissue tropism. The major cellular receptor for LASV is the highly conserved extracellular matrix receptor dystroglycan (DG). Binding of LASV depends on DG's tissue-specific posttranslational modification with the unusual O-linked polysaccharide matriglycan. Read More

    Effector CD8 T cells dedifferentiate into long-lived memory cells.
    Nature 2017 12 13;552(7685):404-409. Epub 2017 Dec 13.
    Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
    Memory CD8 T cells that circulate in the blood and are present in lymphoid organs are an essential component of long-lived T cell immunity. These memory CD8 T cells remain poised to rapidly elaborate effector functions upon re-exposure to pathogens, but also have many properties in common with naive cells, including pluripotency and the ability to migrate to the lymph nodes and spleen. Thus, memory cells embody features of both naive and effector cells, fuelling a long-standing debate centred on whether memory T cells develop from effector cells or directly from naive cells. Read More

    Effect of IL-7 Therapy on Phospho-Ribosomal Protein S6 and TRAF1 Expression in HIV-Specific CD8 T Cells in Patients Receiving Antiretroviral Therapy.
    J Immunol 2018 Jan 8;200(2):558-564. Epub 2017 Dec 8.
    Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada;
    IL-7 therapy has been evaluated in patients who do not regain normal CD4 T cell counts after virologically successful antiretroviral therapy. IL-7 increases total circulating CD4 and CD8 T cell counts; however, its effect on HIV-specific CD8 T cells has not been fully examined. TRAF1, a prosurvival signaling adaptor required for 4-1BB-mediated costimulation, is lost from chronically stimulated virus-specific CD8 T cells with progression of HIV infection in humans and during chronic lymphocytic choriomeningitis infection in mice. Read More

    Revealing the Complexity in CD8 T Cell Responses to Infection in Inbred C57B/6 versus Outbred Swiss Mice.
    Front Immunol 2017 22;8:1527. Epub 2017 Nov 22.
    Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA, United States.
    Recent work has suggested that current mouse models may underrepresent the complexity of human immune responses. While most mouse immunology studies utilize inbred mouse strains, it is unclear if conclusions drawn from inbred mice can be extended to all mouse strains or generalized to humans. We recently described a "surrogate activation marker" approach that could be used to track polyclonal CD8 T cell responses in inbred and outbred mice and noted substantial discord in the magnitude and kinetics of CD8 T cell responses in individual outbred mice following infection. Read More

    Osteoblasts Are Rapidly Ablated by Virus-Induced Systemic Inflammation following Lymphocytic Choriomeningitis Virus or Pneumonia Virus of Mice Infection in Mice.
    J Immunol 2018 Jan 6;200(2):632-642. Epub 2017 Dec 6.
    Priority Research Centre for Healthy Lungs, Department of Microbiology and Immunology, School of Biomedical Sciences and Pharmacy, Faculty of Health and Hunter Medical Research Institute, The University of Newcastle, Callaghan, New South Wales 2305, Australia;
    A link between inflammatory disease and bone loss is now recognized. However, limited data exist on the impact of virus infection on bone loss and regeneration. Bone loss results from an imbalance in remodeling, the physiological process whereby the skeleton undergoes continual cycles of formation and resorption. Read More

    Sustained T follicular helper cell response is essential for control of chronic viral infection.
    Sci Immunol 2017 Dec;2(18)
    Institute of Microbiology, ETH Zürich, Vladimir-Prelog-Weg 4, 8093 Zürich, Switzerland.
    During chronic viral infections, both CD8 and CD4 T cell responses are functionally compromised. Alongside exhaustion of CD8 T cells during chronic viral infections, it has also been documented that the CD4 T cells have an increased propensity to differentiate toward CXCR5 T follicular helper cell (T) lineage. Whether these T cells contribute to the immune response to chronic viral infection has remained unclear. Read More

    A proteomic survey of Junín virus interactions with human proteins reveals host factors required for arenavirus replication.
    J Virol 2017 Nov 29. Epub 2017 Nov 29.
    Department of Medicine, Division of Immunobiology Cellular, Molecular, and Biomedical Sciences Graduate Program Department of Microbiology and Molecular Genetics Department of Biology, University of Vermont, Burlington, VT 05405, USA
    Arenaviruses are negative-strand, enveloped RNA viruses that cause significant human disease. In particular, Junín mammarenvirus (JUNV) is the etiologic agent of Argentine hemorrhagic fever. At present, little is known about the cellular proteins that the arenavirus matrix protein (Z) hijacks to accomplish its various functions, including driving the process of virus release. Read More

    How viruses infiltrate the central nervous system.
    Acta Virol 2017;61(4):393-400
    Central nervous system is protected by the blood-brain barrier, which represents a physical, metabolic and transport barrier and is considered to be a part of a highly dynamic system termed neurovascular unit. Several pathogens, among them viruses, are able to invade the brain. Traversal of viruses across the blood-brain barrier is an essential step for the invasion of the central nervous system and can occur by different mechanisms - by paracellular, transcellular and/or by "Trojan horse" pathway. Read More

    Lymphocytes Negatively Regulate NK Cell Activity via Qa-1b following Viral Infection.
    Cell Rep 2017 Nov;21(9):2528-2540
    Department of Molecular Medicine II, Medical Faculty, Heinrich Heine University, 40225 Düsseldorf, Germany. Electronic address:
    NK cells can reduce anti-viral T cell immunity during chronic viral infections, including infection with the lymphocytic choriomeningitis virus (LCMV). However, regulating factors that maintain the equilibrium between productive T cell and NK cell immunity are poorly understood. Here, we show that a large viral load resulted in inhibition of NK cell activation, which correlated with increased expression of Qa-1b, a ligand for inhibitory NK cell receptors. Read More

    Critical Role for Very-Long Chain Sphingolipids in Invariant Natural Killer T Cell Development and Homeostasis.
    Front Immunol 2017 1;8:1386. Epub 2017 Nov 1.
    Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel.
    The role of sphingolipids (SLs) in the immune system has come under increasing scrutiny recently due to the emerging contributions that these important membrane components play in regulating a variety of immunological processes. The acyl chain length of SLs appears particularly critical in determining SL function. Here, we show a role for very-long acyl chain SLs (VLC-SLs) in invariant natural killer T (NKT) cell maturation in the thymus and homeostasis in the liver. Read More

    The Loss of TET2 Promotes CD8 T Cell Memory Differentiation.
    J Immunol 2018 01 17;200(1):82-91. Epub 2017 Nov 17.
    Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;
    T cell differentiation requires appropriate regulation of DNA methylation. In this article, we demonstrate that the methylcytosine dioxygenase ten-eleven translocation (TET)2 regulates CD8 T cell differentiation. In a murine model of acute viral infection, TET2 loss promotes early acquisition of a memory CD8 T cell fate in a cell-intrinsic manner without disrupting Ag-driven cell expansion or effector function. Read More

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