By a serial transcriptomic analysis and biomarker-based tracking of nasopharyngeal samples from SARS-CoV-2 infected individuals, it was found that interferon stimulated genes (ISGs) induction was correlated with the increasing virus titer. The ISGs induction rose with viral replication and peaked just as viral load began to decline. By using lung organoid-infection model, it was shown that rhinovirus infection prior to SARS-CoV-2 infection, which caused acceleration of ISGs response, prevented SARS-CoV-2 replication. Moreover, blocking of ISGs induction by a IRF-3 nuclear-translocation inhibitor BX795 enhanced SARS-CoV-2 replication. The activity of ISGs-mediated immune response prevents early SARS-CoV-2 replication.
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