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Acute viral infections are typically cleared by the host’s immune system, but certain RNA viruses can establish ‘within host’ persistent infections, for example in the central nervous system (CNS). Neurons within the CNS are a potential site for viral persistence due to the limited capacity of the host to deploy cytolytic and inflammatory defenses in this environment. Subacute sclerosing panencephalitis (SSPE) is a rare but fatal disease caused by persistent infection with measles virus (MeV), often occurring years after acute measles. Despite the availability of effective vaccines, SSPE remains a concern due to vaccine hesitancy and disruptions in vaccination programs.