ISG15 and viral infectious disease: For example, a meta2cell enriched in patients soon after infection (metacell A) contains cells in an early activation state distinguished by the expression of NF-κB response genes, IFN-α receptor subunit IFNAR2 and downstream interferon-stimulated genes (IRF7, IRF9, ISG15 and IFITM1), reflecting T cell responsiveness to type I IFN, a cytokine associated with viral infections and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathology53 (Fig. 6e).