Project description:To identify mechanisms behind immunosuppression during virus infections, we infected mice with LCMV-Armstrong and LCMV-Clone 13 expression patterns. LCMV-Armstrong induces a T-cell reaction that resolves infection within 8-10 days, while LCMV-Clone13 generates a persisten infection through immunosuppression. We used microarray to uncover splenic gene expression patterns specific to each LCMV infection at 5, 9, and 30 days C57BL6 mice, 6-10 weeks old, were infected with LCMV-Armstrong and LCMV-Clone 13 or left uninfected (naïve). At days 5, 9, and 30 whole spleens were harvested for RNA extraction and hybridization on Affymetric microarray.
Project description:To identify mechanisms behind immunosuppression during virus infections, we infected mice with LCMV-Armstrong and LCMV-Clone 13 expression patterns. LCMV-Armstrong induces a T-cell reaction that resolves infection within 8-10 days, while LCMV-Clone13 generates a persisten infection through immunosuppression. We used microarray to uncover splenic gene expression patterns specific to each LCMV infection at 5, 9, and 30 days
Project description:The goal of this study was to identify the molecular programming using ATAC-seq of CD8 T cells responding to different viral infections. Mice were infected with either LCMV Armstrong to model an acute infection or LCMV Clone-13 to model a chronic infection. At various time points following infection, virus-specific CD8 T cells were purified and ATAC-seq performed. These data identify the changes in chromatin accessibility associated with acute infections and the establishment of functional memory versus those accessibility changes associated with chronic infection.
Project description:Lymphocytic choriomeningitis virus (LCMV) is the prototypic arenavirus and a natural mouse pathogen. LCMV Armstrong, an acutely resolved strain, and LCMV Clone 13, a mutant that establishes chronic infection, have provided contrasting infection models that continue to inform the fundamental biology of T cell differentiation, regulation of exhaustion, and response to checkpoint blockade. Here, we report the isolation and characterization of LCMV Minnesota (LCMV-MN), which was naturally transmitted to laboratory mice upon cohousing with pet shop mice and shares 80-95% amino acid homology with previously characterized LCMV strains. Infection of laboratory mice with purified LCMV-MN resulted in viral persistence that was intermediate between LCMV Armstrong and Clone 13, with widely disseminated viral replication and viremia that was controlled within 15-30 days, unless CD4 T cells were depleted prior to infection. LCMV-MN responding CD8+ T cells biased differentiation towards the recently described PD1+ CXCR5+ Tim-3lo stem-like CD8+ T cell population (also referred to as T exhausted progenitors, Tpex) that effectuates responses to PD-1 blockade checkpoint inhibition, a therapy that rejuvenates responses against chronic infections and cancer. This subset resembled previously characterized PD1+ TCF1+ stem-like CD8+ T cells by transcriptional, phenotypic, and functional assays, yet was atypically abundant. LCMV-MN may provide a tool to better understand the breadth of immune responses in different settings of chronic antigen stimulation as well as the ontogeny of T exhausted progenitors and the regulation of responsiveness to PD-1 blockade.
