RING finger protein 5 is a key anti-FMDV host factor through inhibition of virion assembly

Recent research identifies RNF5 as a critical host protein that naturally limits the replication of the foot-and-mouth disease virus (FMDV). By acting as an E3 ubiquitin ligase, RNF5 attaches ubiquitin chains to the viral VP1 protein at a specific site called Lys200, marking it for destruction via the cell's proteasome. This degradation effectively disrupts the assembly of new virions, thereby reducing the overall viral load and the severity of the disease. Experiments using knockout mice and modified viruses confirmed that the absence of this protein or its target site leads to significantly higher infection rates and organ damage. Furthermore, the study suggests that a pharmacological activator called Analog-1 can boost this natural defense to treat infections. Because RNF5 also targets the structural proteins of other picornaviruses, such as Poliovirus and Enterovirus 71, it represents a promising target for developing broad-spectrum antiviral therapies.