SSC-miR-221-3p acts as a host barrier to regulate nuclear factor kappa B (NF-κB) P65 phosphorylation, inhibit the expression of anti-apoptotic protein HMBOX1, and induce apoptosis during the cross-species infection of IAV, or by targeting and silencing the hemagglutinin (HA) gene of the H5 subtype, restricting the infection and replication of influenza viruses [38]. This evidence concerns the gene HMBOX1 and infection.