Differential roles of HSP70 and HSP90 in Senecavirus A infection: IRES-dependent translational regulation and viral replication mechanisms.

As opportunistic intracellular pathogens, viruses rely on numerous sequential interactions between host and viral factors for their replication. Given the significance of molecular chaperones (heat shock protein 70 and heat shock protein 90) in mediating protein homeostasis, research has suggested that they are involved in viral infections in many ways. This study explored the roles of HSP70 and HSP90 in the Senecavirus A (SVA) life cycle. We demonstrate that HSP70 and HSP90 regulate virus internal ribosome entry site (IRES)-dependent translation activity by acting on SVA IRES. Additionally, we show that HSP70 promotes SVA IRES-dependent translation through association with SVA IRES domain II, and HSP90 may function through interaction with SVA IRES domain IV. Furthermore, we found that the structural proteins and four non-structural proteins (Lpro, 2B, 2C, 3A) were shown to interact with HSP70 and HSP90. Furthermore, we determined that HSP70 and Hsp90 activity is important for virus replication by stabilizing SVA proteins and preventing their degradation via the ubiquitin-proteasome, apoptosis, and autophagy-lysosome pathway. Our findings indicate that HSP70 and HSP90 activity is essential for SVA replication, offering new insights into the development of potential specific control strategies against SVA infection.