scholarly journals Viral Infections and Autoimmune Disease: Roles of LCMV in Delineating Mechanisms of Immune Tolerance

Viruses ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 885
Author(s):  
Georgia Fousteri ◽  
Amy Dave Jhatakia
Keyword(s):  
Immune System ◽  
Autoimmune Disease ◽  
Viral Infections ◽  
Molecular Mimicry ◽  
Short Review ◽  
Organ Damage ◽  
Lymphocytic Choriomeningitis ◽  
Immune Deviation ◽  
Viral Pathogen ◽  
Lcmv Infection

Viral infections are a natural part of our existence. They can affect us in many ways that are the result of the interaction between the viral pathogen and our immune system. Most times, the resulting immune response is beneficial for the host. The pathogen is cleared, thus protecting our vital organs with no other consequences. Conversely, the reaction of our immune system against the pathogen can cause organ damage (immunopathology) or lead to autoimmune disease. To date, there are several mechanisms for virus-induced autoimmune disease, including molecular mimicry and bystander activation, in support of the “fertile field” hypothesis (terms defined in our review). In contrast, viral infections have been associated with protection from autoimmunity through mechanisms that include Treg invigoration and immune deviation, in support of the “hygiene hypothesis”, also defined here. Infection with lymphocytic choriomeningitis virus (LCMV) is one of the prototypes showing that the interaction of our immune system with viruses can either accelerate or prevent autoimmunity. Studies using mouse models of LCMV have helped conceive and establish several concepts that we now know and use to explain how viruses can lead to autoimmune activation or induce tolerance. Some of the most important mechanisms established during the course of LCMV infection are described in this short review.

scholarly journals Viral Infections and Autoimmune Disease: Roles of LCMV in Delineating Mechanisms of Immune Tolerance

2019 ◽  
Author(s):  
Georgia Fousteri ◽  
Amy Dave Jhatakia
Keyword(s):  
Immune System ◽  
Autoimmune Disease ◽  
Viral Infections ◽  
Molecular Mimicry ◽  
Short Review ◽  
Hygiene Hypothesis ◽  
Organ Damage ◽  
Lymphocytic Choriomeningitis ◽  
Immune Deviation ◽  
Viral Pathogen

Viral infections are a natural part of our existence. They can affect us in many ways that are the result of the interaction between the viral pathogen and our immune system. Most times the resulting immune response is beneficial for the host. The pathogen gets cleared thus protecting our vital organs with no other consequences. Conversely, the reaction of our immune system against the pathogen can cause organ damage (immunopathology) or lead to autoimmune disease. To date, there are several mechanisms for virus-induced autoimmune disease, including molecular mimicry and bystander activation, in support of the “fertile field” hypothesis, terms defined in our review. On the flip side, viral infections have been associated with protection from autoimmunity through mechanisms that include Treg invigoration and immune deviation, in support of the “hygiene hypothesis”, also defined here. Infection with lymphocytic choriomeningitis virus (LCMV) is one of the prototypes showing that the interaction of our immune system with viruses can either accelerate or prevent autoimmunity. Studies using mouse models of LCMV have helped conceive and establish several concepts that we today know and explain how viruses can lead to autoimmune activation or induce tolerance. Some of the most important mechanisms established during the course LCMV are described in this short review.

scholarly journals Viral Infections and Autoimmune Disease: Roles of LCMV in Delineating Mechanisms of Immune Tolerance

2019 ◽  
Author(s):  
Georgia Fousteri
Keyword(s):  
Immune System ◽  
Autoimmune Disease ◽  
Viral Infections ◽  
Molecular Mimicry ◽  
Short Review ◽  
Hygiene Hypothesis ◽  
Organ Damage ◽  
Lymphocytic Choriomeningitis ◽  
Immune Deviation ◽  
Viral Pathogen

Viral infections make a natural part of our existence. They can affect us in hundreds of different ways that are the result of the interaction between the viral pathogen and our immune system. Most times the resulting immune response is beneficial for the host. The pathogen gets cleared protecting our vital organs with no other consequences. Sometimes, things go wrong and the reaction of our immune system against the pathogen causes organ damage (immunopathology) or leads to autoimmune disease. To date, there are several mechanisms for virus-induced autoimmune disease, including molecular mimicry and bystander activation, in support of the “fertile field” hypothesis. On the flip side, viral infections have been associated with protection from autoimmunity through mechanisms that include Treg invigoration and immune deviation, in support of the “hygiene hypothesis”. Infection with lymphocytic choriomeningitis virus (LCMV) is one of the prototype viral systems showing that the interaction of our immune system with the viruses can either accelerate or prevent autoimmunity. Studies using LCMV have helped conceive and establish several concepts that we today know and explain how viruses can lead to autoimmune activation or induce tolerance. Some of the most important mechanisms established in LCMV are described in this short review.

scholarly journals Hesperidin and SARS-CoV-2: New Light on the Healthy Functions of Citrus Fruit

2020 ◽  
Author(s):  
Paolo Bellavite ◽  
Alberto Donzelli
Keyword(s):  
Immune System ◽  
Citrus Sinensis ◽  
Viral Infections ◽  
Citrus Fruit ◽  
Short Review ◽  
Citrus Fruits ◽  
Early Proteins ◽  
Main Protease ◽  
The Many

Among the many approaches to COVID-19 prevention, the possible role of diet has so far been somewhat marginal. Nutrition is very rich in substances with a potential beneficial effect on health and some of these could have an antiviral action or in any case be important in modulating the immune system and in defending cells from the oxidative stress associated with infection. This short review draws the attention on some components of Citrus fruits and especially of the orange (Citrus sinensis), well known for its vitamin content, but less for the function of its flavonoids. Among the latter, hesperidin has recently attracted the attention of researchers, because it binds to the key proteins of the SARS-CoV-2 virus. Several computational methods, independently applied by different researchers, showed that hesperidin has a low binding energy both with the coronavirus "spike" protein, and with the main protease that transforms the early proteins of the virus (pp1a and ppa1b) into the complex responsible for viral replication. The affinity of hesperidin for these proteins is comparable if not superior to that of common chemical antivirals. The preventive efficacy of vitamin C, at dosage attainable by diet, against viral infections is controversial, but recent reviews suggest that this substance may be useful in case of increased stress on the immune system. Finally, the reasons that suggest undertaking appropriate research on the Citrus fruits addition in the diet, as a complementary prevention and treatment of COVID-19, are discussed.

scholarly journals Systemic Sclerosis Pathogenesis and Emerging Therapies, beyond the Fibroblast

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Andrea Sierra-Sepúlveda ◽  
Alexia Esquinca-González ◽  
Sergio A. Benavides-Suárez ◽  
Diego E. Sordo-Lima ◽  
Adrián E. Caballero-Islas ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Immune System ◽  
Systemic Sclerosis ◽  
Autoimmune Disease ◽  
State Of The Art ◽  
Therapeutic Targets ◽  
Organ Damage ◽  
The State ◽  
Pathogenic Mechanism ◽  
Emerging Therapies

Systemic sclerosis (SSc) is a complex rheumatologic autoimmune disease in which inflammation, fibrosis, and vasculopathy share several pathogenic pathways that lead to skin and internal organ damage. Recent findings regarding the participation and interaction of the innate and acquired immune system have led to a better understanding of the pathogenesis of the disease and to the identification of new therapeutic targets, many of which have been tested in preclinical and clinical trials with varying results. In this manuscript, we review the state of the art of the pathogenesis of this disease and discuss the main therapeutic targets related to each pathogenic mechanism that have been discovered so far.

scholarly journals Pemphigus Vulgaris Following Influenza: A Case Report

2019 ◽  
Vol 3 (6) ◽  
pp. 418-422
Author(s):  
Kristen Bice ◽  
Channing Hood ◽  
Rawaa Almukhtar ◽  
Michelle Gerdes ◽  
Pamela Martin ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Case Report ◽  
Autoimmune Disease ◽  
Influenza Vaccine ◽  
Mucous Membrane ◽  
Influenza A ◽  
Viral Infections ◽  
Molecular Mimicry ◽  
Pemphigus Vulgaris ◽  
Epitope Spreading

Viruses have long been implicated as potential triggers of autoimmune disease. In the case of pemphigus vulgaris, members of the herpesviridae family are often associated with its development. There have also been reports of pemphigus being triggered by the influenza vaccine. We report a case of a 17-year-old male who developed mucous membrane-predominant pemphigus vulgaris after testing positive for the influenza virus and discuss proposed hypotheses for the association between viral infections and autoimmunity, such as molecular mimicry and epitope spreading.

scholarly journals High numbers of IL-2-producing CD8+ T cells during viral infection: correlation with stable memory development

2002 ◽  
Vol 83 (9) ◽  
pp. 2123-2133 ◽  
Author(s):  
Nanna Ny Kristensen ◽  
Jan Pravsgaard Christensen ◽  
Allan Randrup Thomsen
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mhc Class Ii ◽  
Viral Infections ◽  
Cell Subset ◽  
Lymphocytic Choriomeningitis ◽  
Model Systems ◽  
Loss Of Function ◽  
Ifn Γ ◽  
Lcmv Infection

Using infections with lymphocytic choriomeningitis virus (LCMV) and vesicular stomatitis virus in mice as model systems, we have investigated the ability of antigen-primed CD8+ T cells generated in the context of viral infections to produce IL-2. Our results indicate that acute immunizing infection normally leads to generation of high numbers of IL-2-producing antigen-specific CD8+ T cells. By costaining for IL-2 and IFN-γ intracellularly, we found that IL-2-producing cells predominantly constitute a subset of cells also producing IFN-γ. Comparison of the kinetics of generation revealed that IL-2-producing cells appear slightly delayed compared with the majority of IFN-γ producing cells, and the relative frequency of the IL-2-producing subset increases with transition into the memory phase. In contrast to acute immunizing infection, few IL-2-producing cells are generated during chronic LCMV infection. Furthermore, in MHC class II-deficient mice, which only transiently control LCMV infection, IL-2-producing CD8+ T cells are initially generated, but by 4 weeks after infection this subset has nearly disappeared. Eventually the capacity to produce IFN-γ also becomes impaired, while cell numbers are maintained at a level similar to those in wild-type mice controlling the infection. Taken together, these findings indicate that phenotyping of T cell populations based on capacity to produce cytokines, and especially IL-2, can provide important information as to the functional status of the analysed cell subset. Specifically, combined analysis of the capacity to produce IL-2 and IFN-γ can be used as a predictor for loss of function within the CD8+ T cell compartment.

scholarly journals Profiling virus-specific Tcf1+ T cell repertoires during acute and chronic viral infection

2020 ◽  
Author(s):  
Alexander Yermanos ◽  
Ioana Sandu ◽  
Alessandro Pedrioli ◽  
Mariana Borsa ◽  
Franziska Wagen ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Viral Infections ◽  
Clonal Diversity ◽  
Cell Receptor ◽  
Lymphocytic Choriomeningitis ◽  
Tcr Repertoire ◽  
Repertoire Sequencing ◽  
Lcmv Infection

AbstractCD8 T cells play a crucial role in providing protection from viral infections. It has recently been established that a subset of CD8 T cells expressing Tcf1 are responsible for sustaining exhausted T cells during chronic lymphocytic choriomeningitis virus (LCMV) infection. Many of these studies, however, have been performed using T cell receptor (TCR) transgenic mice, in which CD8 T cells express a monoclonal TCR specific for the LCMV glycoprotein. To investigate whether the Tcf1+ and Tcf1-repertoires are naturally composed of similar or different clones in wild-type mice exposed to acute or chronic LCMV infection, we performed TCR repertoire sequencing of virus-specific CD8 T cells, including Tcf1+ and Tcf1-populations. Our analysis revealed that the Tcf1+ TCR repertoire is maintained at an equal or higher degree of clonal diversity despite harboring fewer cells. Additionally, within the same animal, there was extensive clonal overlap between the Tcf1+ and Tcf1-repertoires in both chronic and acute LCMV infection. We could further detect these virus-specific clones in longitudinal blood samples earlier in the infection. With respect to common repertoire parameters (clonal overlap, germline gene usage, and clonal expansion), we found minor differences between the virus-specific TCR repertoire of acute and chronic LCMV infection 40 days post infection. Overall, our results indicate that the Tcf1+ population emerging during chronic LCMV infection is not clonally distinct from the Tcf1-population, supporting the notion that the Tcf1+ pool is indeed a fuel for the more exhausted Tcf1-population within the heterogenous repertoire of LCMV-specific CD8 T cells.

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

Viruses ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 106 ◽  
Author(s):  
Mohamed Abdel-Hakeem
Keyword(s):  
Major Histocompatibility Complex ◽  
Immune System ◽  
Essential Role ◽  
Viral Infections ◽  
Lymphocytic Choriomeningitis ◽  
Lymphocytic Choriomeningitis Virus ◽  
Viral Escape ◽  
Escape Mutation ◽  
Histocompatibility Complex

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. In addition, we discuss related discoveries such as development of tetramers, viral escape mutation, and the phenomenon of T-cell exhaustion.

Enhancing FcγR-mediated antibody effector function during persistent viral infection

2018 ◽  
Vol 3 (27) ◽  
pp. eaao3125 ◽  
Author(s):  
Andreas Wieland ◽  
Alice O. Kamphorst ◽  
Rajesh M. Valanparambil ◽  
Jin-Hwan Han ◽  
Xiaojin Xu ◽  
...  
Keyword(s):  
Viral Infections ◽  
Lymphocytic Choriomeningitis ◽  
Target Cells ◽  
Therapeutic Antibodies ◽  
Persistently Infected ◽  
Effector Functions ◽  
Persistent Viral Infection ◽  
Wide Range ◽  
Persistent Viral Infections ◽  
Lcmv Infection

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. Efficient antibody-mediated depletion during persistent LCMV infection required increased levels of antibody bound to target cells or use of afucosylated antibodies with increased affinity for FcγRs. Antibodies targeting the highly expressed CD90 antigen or overexpressed human CD20 efficiently depleted their target cells in naïve and persistently infected mice, whereas antibodies directed against less abundant antigens failed to deplete their target cells during persistent LCMV infection. In addition, we demonstrate the superior activity of afucosylated antibodies in the presence of endogenous ICs. We generated afucosylated antibodies directed against CD4 and CD8α, which, in contrast to their parental fucosylated versions, efficiently depleted their respective target cells in persistently infected mice. Efficient antibody-mediated depletion can thus be achieved if therapeutic antibodies can outcompete endogenous ICs for access to FcγRs either by targeting highly expressed antigens or by increased affinity for FcγRs. Our findings have implications for the optimization of therapeutic antibodies and provide strategies to allow efficient FcγR engagement in the presence of competing endogenous ICs in persistent viral infections, autoimmune diseases, and cancer.

scholarly journals Viral Infection of Transgenic Mice Expressing a Viral Protein in Oligodendrocytes Leads to Chronic Central Nervous System Autoimmune Disease

1996 ◽  
Vol 184 (6) ◽  
pp. 2371-2384 ◽  
Author(s):  
Claire F. Evans ◽  
Marc S. Horwitz ◽  
Monte V. Hobbs ◽  
Michael B.A. Oldstone
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Autoimmune Disease ◽  
Transgenic Mice ◽  
Molecular Mimicry ◽  
Lymphocytic Choriomeningitis ◽  
Motor Dysfunction ◽  
Specific Memory ◽  
Intraperitoneal Infection ◽  
Antigenic Epitopes

One hypothesis for the etiology of central nervous system (CNS) autoimmune disease is that infection by a virus sharing antigenic epitopes with CNS antigens (molecular mimicry) elicits a virus-specific immune response that also recognizes self-epitopes. To address this hypothesis, transgenic mice were generated that express the nucleoprotein or glycoprotein of lymphocytic choriomeningitis virus (LCMV) as self in oligodendrocytes. Intraperitoneal infection with LCMV strain Armstrong led to infection of tissues in the periphery but not the CNS, and the virus was cleared within 7–14 d. After clearance, a chronic inflammation of the CNS resulted, accompanied by upregulation of CNS expression of MHC class I and II molecules. A second LCMV infection led to enhanced CNS pathology, characterized by loss of myelin and clinical motor dysfunction. Disease enhancement also occurred after a second infection with unrelated viruses that cross-activated LCMV-specific memory T cells. These findings indicate that chronic CNS autoimmune disease may be induced by infection with a virus sharing epitopes with a protein expressed in oligodendrocytes and this disease may be enhanced by a second infection with the same or an unrelated virus. These results may explain the association of several different viruses with some human autoimmune diseases.

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