A picorna-like virus suppresses the N-end rule pathway to inhibit apoptosis

The N-end rule pathway is an evolutionarily conserved proteolytic system that degrades proteins containing N-terminal degradation signals called N-degrons, and has emerged as a key regulator of various processes. Viruses manipulate diverse host pathways to facilitate viral replication and evade Antiviral defenses. However, it remains unclear if viral Infection has any impact on the N-end rule pathway. Here, using a picorna-like virus as a model, we found that viral Infection promoted the accumulation of caspase-cleaved Drosophila inhibitor of Apoptosis 1 (DIAP1) by inducing the degradation of N-terminal amidohydrolase 1 (NTAN1), a key N-end rule component that identifies N-degron to initiate the process. The virus-induced NTAN1 degradation is independent of polyubiquitylation but dependent on Proteasome. Furthermore, the virus-induced N-end rule pathway suppression inhibits Apoptosis and benefits viral replication. Thus, our findings demonstrate that a virus can suppress the N-end rule pathway, and uncover a new mechanism for virus to evade Apoptosis.