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Viruses
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LCMV – A Pillar for Immunology Research
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LCMV – A Pillar for Immunology Research

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (30 June 2019) | Viewed by 22626

Special Issue Editor

Dr. Markus J. Hofer

E-Mail Website
Guest Editor
School of Life and Environmental Sciences, The University of Sydney, Sydney, Australia
Interests: neuroimmunology; neuropathology; neuroinflammation; antiviral responses

Special Issue Information

Dear Colleagues,

Since its original description by Charles Armstrong in 1934, lymphocytic choriomeningitis virus (LCMV) has been a useful instrument in the immunologists’ toolbox. LCMV has been central to the discovery of a wide range of immunological concepts, both relevant to the antiviral host response and beyond. They include ground-breaking experiments by Rolf Zinkernagel and Peter Doherty that led to the discovery of MHC molecules and ultimately the concept of self tolerance, and Michael Oldstone’s work on viral immunopathology and chronic infection. Likewise, the seminal works of Rafi Ahmed, E. John Wherry and many others to characterise functional T cell exhaustion laid the foundation for the development of new treatments for chronic infections and malignant diseases. There is no doubt that the study of LCMV will continue to open new avenues of research in immunology.

The goal of this Special Issue is to assemble both reviews and original research manuscripts that focus on LCMV as both a model and pathogen to illuminate the diverse nature of anti-viral responses.

Dr. Markus J. Hofer
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Lymphocytic choriomeningitis virus
  • LCMV
  • Acute versus chronic infection
  • Innate antiviral response
  • Adaptive antiviral response
  • Immune cell exhaustion
  • CNS infection and neurological disease
  • Human infection

Published Papers (4 papers)

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Research

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22 pages, 4575 KiB  
Article
Viral Strain Determines Disease Symptoms, Pathology, and Immune Response in Neonatal Rats with Lymphocytic Choriomeningitis Virus Infection
by Jeffrey M. Plume, Dylan Todd and Daniel J. Bonthius
Viruses 2019, 11(6), 552; https://doi.org/10.3390/v11060552 - 14 Jun 2019
Cited by 7 | Viewed by 4185
Abstract
When infection with lymphocytic choriomeningitis (LCMV) occurs during pregnancy, the virus can infect the fetus and injure the fetal brain. However, type, location, and severity of neuropathology differ among cases. One possible explanation for this diversity is that fetuses are infected with different [...] Read more.
When infection with lymphocytic choriomeningitis (LCMV) occurs during pregnancy, the virus can infect the fetus and injure the fetal brain. However, type, location, and severity of neuropathology differ among cases. One possible explanation for this diversity is that fetuses are infected with different viral strains. Using a rat model of congenital LCMV infection, we investigated how differences in LCMV strain (E350, WE2.2, and Clone 13) affect outcome. Rat pups received intracranial inoculations on postnatal day 4. E350 initially targeted glial cells, while WE2.2 and Clone 13 targeted neurons. The E350 strain induced focal destructive lesions, while the other strains induced global microencephaly. E350 attracted large numbers of CD8+ lymphocytes early in the disease course, while Clone 13 attracted CD4+ lymphocytes, and the infiltration occurred late. The E350 and WE2.2 strains induced large increases in expression of pro-inflammatory cytokines, while Clone 13 did not. The animals infected with E350 and WE2.2 became ataxic and performed poorly on the negative geotaxis assay, while the Clone 13 animals had profound growth failure. Thus, in the developing brain, different LCMV strains have different patterns of infection, neuropathology, immune responses and disease symptoms. In humans, different outcomes from congenital LCMV may reflect infection with different strains. Full article
(This article belongs to the Special Issue LCMV – A Pillar for Immunology Research)
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Review

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11 pages, 542 KiB  
Review
Viral Infections and Autoimmune Disease: Roles of LCMV in Delineating Mechanisms of Immune Tolerance
by Georgia Fousteri and Amy Dave Jhatakia
Viruses 2019, 11(10), 885; https://doi.org/10.3390/v11100885 - 21 Sep 2019
Cited by 6 | Viewed by 4679
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue LCMV – A Pillar for Immunology Research)
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20 pages, 1512 KiB  
Review
Complexities of Type I Interferon Biology: Lessons from LCMV
by Tamara Suprunenko and Markus J. Hofer
Viruses 2019, 11(2), 172; https://doi.org/10.3390/v11020172 - 20 Feb 2019
Cited by 19 | Viewed by 5367
Abstract
Over the past decades, infection of mice with lymphocytic choriomeningitis virus (LCMV) has provided an invaluable insight into our understanding of immune responses to viruses. In particular, this model has clarified the central roles that type I interferons play in initiating and regulating [...] Read more.
Over the past decades, infection of mice with lymphocytic choriomeningitis virus (LCMV) has provided an invaluable insight into our understanding of immune responses to viruses. In particular, this model has clarified the central roles that type I interferons play in initiating and regulating host responses. The use of different strains of LCMV and routes of infection has allowed us to understand how type I interferons are critical in controlling virus replication and fostering effective antiviral immunity, but also how they promote virus persistence and functional exhaustion of the immune response. Accordingly, these discoveries have formed the foundation for the development of novel treatments for acute and chronic viral infections and even extend into the management of malignant tumors. Here we review the fundamental insights into type I interferon biology gained using LCMV as a model and how the diversity of LCMV strains, dose, and route of administration have been used to dissect the molecular mechanisms underpinning acute versus persistent infection. We also identify gaps in the knowledge regarding LCMV regulation of antiviral immunity. Due to its unique properties, LCMV will continue to remain a vital part of the immunologists’ toolbox. Full article
(This article belongs to the Special Issue LCMV – A Pillar for Immunology Research)
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26 pages, 2478 KiB  
Review
Immune Exhaustion: Past Lessons and New Insights from Lymphocytic Choriomeningitis Virus
by Shannon M. Kahan and Allan J. Zajac
Viruses 2019, 11(2), 156; https://doi.org/10.3390/v11020156 - 13 Feb 2019
Cited by 25 | Viewed by 7718
Abstract
Lymphocytic choriomeningitis virus (LCMV) is a paradigm-forming experimental system with a remarkable track record of contributing to the discovery of many of the fundamental concepts of modern immunology. The ability of LCMV to establish a chronic infection in immunocompetent adult mice was instrumental [...] Read more.
Lymphocytic choriomeningitis virus (LCMV) is a paradigm-forming experimental system with a remarkable track record of contributing to the discovery of many of the fundamental concepts of modern immunology. The ability of LCMV to establish a chronic infection in immunocompetent adult mice was instrumental for identifying T cell exhaustion and this system has been invaluable for uncovering the complexity, regulators, and consequences of this state. These findings have been directly relevant for understanding why ineffective T cell responses commonly arise during many chronic infections including HIV and HCV, as well as during tumor outgrowth. The principal feature of exhausted T cells is the inability to elaborate the array of effector functions necessary to contain the underlying infection or tumor. Using LCMV to determine how to prevent and reverse T cell exhaustion has highlighted the potential of checkpoint blockade therapies, most notably PD-1 inhibition strategies, for improving cellular immunity under conditions of antigen persistence. Here, we discuss the discovery, properties, and regulators of exhausted T cells and highlight how LCMV has been at the forefront of advancing our understanding of these ineffective responses. Full article
(This article belongs to the Special Issue LCMV – A Pillar for Immunology Research)
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