The recombinant engineering of trisegmented lymphocytic choriomeningitis virus (LCMV) to express two genes of interest was recently reported. We used this technology to efficiently express green fluorescent protein (GFP) and the immunoregulatory gene product interleukin-10 (IL-10) in vitro, assess IL-10 function in vivo during viral meningitis, and generate specific, robust monoclonal antibody responses to IL-10. Tripartite viruses were attenuated in wild-type and TLR7(-/-) mice. However, IFNAR1(-/-) mice sustained systemic viral replication when 2 nucleotide substitutions from a persistent LCMV variant were present. These findings demonstrate the utility of tripartite LCMV in vitro and in vivo to study genes in the context of a well-defined model system.
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http://dx.doi.org/10.1128/JVI.00486-11 | DOI Listing |
Front Immunol
March 2023
Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, United States.
Introduction: Tuberculosis (TB) caused by remains a major global health threat. The only available vaccine Bacille Calmette-Guérin (BCG) does not prevent adult pulmonary TB. New effective TB vaccines should aim to stimulate robust T cell responses in the lung mucosa to achieve high protective efficacy.
View Article and Find Full Text PDFMethods Mol Biol
July 2022
Texas Biomedical Research Institute, San Antonio, TX, USA.
Reverse genetics systems provide a powerful tool to generate recombinant arenavirus expressing reporters to facilitate the investigation of the arenavirus life cycle and also for the discovery of antiviral countermeasures. The plasmid-encoded viral ribonucleoprotein components initiate the transcription and replication of a plasmid-driven full-length viral genome, resulting in infectious virus. Thereby, this approach is ideal for the generation of recombinant arenaviruses expressing reporter genes that can be used as valid surrogates for virus replication.
View Article and Find Full Text PDFElife
March 2021
Immune Cell Biology Laboratory, Department of Biomedicine, University of Basel, University Hospital Basel, Basel, Switzerland.
A hallmark of adaptive immunity is CD4 T cells' ability to differentiate into specialized effectors. A long-standing question is whether T cell receptor (TCR) signal strength can dominantly instruct the development of Th1 and T follicular helper (Tfh) cells across distinct infectious contexts. We characterized the differentiation of murine CD4 TCR transgenic T cells responding to altered peptide ligand lymphocytic choriomeningitis viruses (LCMV) derived from acute and chronic parental strains.
View Article and Find Full Text PDFNat Commun
February 2021
Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
Self-reactive CD8 T cells are important mediators of progressive tissue damage in autoimmune diseases, but the molecular program underlying these cells' functional adaptation is unclear. Here we characterize the transcriptional and epigenetic landscape of self-reactive CD8 T cells in a mouse model of protracted central nervous system (CNS) autoimmunity and compare it to populations of CNS-resident memory CD8 T cells emerging from acute viral infection. We find that autoimmune CD8 T cells persisting at sites of self-antigen exhibit characteristic transcriptional regulation together with distinct epigenetic remodeling.
View Article and Find Full Text PDFViruses
January 2021
Center for Predictive Medicine for Biodefense and Emerging Infectious diseases, University of Louisville, Louisville, KY 40202, USA.
Defective interfering particles (DIPs) are naturally occurring products during virus replication in infected cells. DIPs contain defective viral genomes (DVGs) and interfere with replication and propagation of their corresponding standard viral genomes by competing for viral and cellular resources, as well as promoting innate immune antiviral responses. Consequently, for many different viruses, including mammarenaviruses, DIPs play key roles in the outcome of infection.
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