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?:abstract
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Neurotropic virus induced neuroinflammation initiates with the activation of brain resident immune cells which causes a heightened release of chemokines/cytokines leading to a compromise in the blood brain barrier integrity This accentuates the upregulation of regulatory molecules like antiviral Interferon stimulating gene induced tetratricopeptide repeats protein, Ifit2, and augments infiltration of peripheral immune cells Among the early infiltrating immune cells, a large population is composed of neutrophils and monocyte/macrophages which, along with brain resident microglia, orchestrate the full panoply of innate immune responses Ifit2 has been shown to be beneficial in protecting mice from lethal neurotropic virus infection by restricting viral replication and amplifying antiviral responses Using a murine neurotropic coronavirus infection in Ifit2-/- mice, we report that in the absence of Ifit2, viral replication is significantly increased and mice develop severe neuropathy Despite the enormous viral load, Ifit2-deficient mice are impaired in microglial activation and recruitment of peripheral T cells into the CNS To further confirm the role of migratory T cells in viral-induced neuroinflammation and neurodegeneration, studies were conducted in CD4-/- mice Results showed no significant change in acute stage pathogenesis, whereas CD4-/- mice showed accelerated loss of axon-myelin coherence during the chronic stage Together, studies in Ifit2 and CD4 knockout mice reveal that the interplay between brain resident microglia and migratory helper T cells is important for strengthening host immunity against neurotropic virus infection
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