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4 Viral interference and innate mucosal priming: a paradigm shift Recent translational evidence demonstrates that early epithelial interferon-stimulated genes (ISG) programs can limit SARS-CoV-2 infection independently of adaptive immunity, underscoring the biological plausibility of mechanisms acting at the mucosal surface prior to viral establishment ( One such mechanism is viral interference, a well-described phenomenon in respiratory virology, whereby infection or exposure to one virus can transiently reduce susceptibility to infection by another virus, often through interferon-mediated antiviral states in host cells ( Importantly, not all interferon responses are equivalent