Previous studies have indicated that IPS-1 reduction can arise via multiple, non-mutually exclusive mechanisms: host-mediated ubiquitination and proteasomal turnover driven by PCBP2 recruitment of the HECT-type E3 ligase AIP446; direct proteolytic cleavage by viral proteases, which displace or fragment mitochondrial IPS-147; functional inhibition by viral accessory proteins that block IPS-1–RIG-I interactions48; infection-induced microRNAs that repress IPS-1 transcripts46; and apoptosis-associated caspase cleavage of IPS-1.47 Here, PCBP2 is linked to infection.