The leader proteinase of foot-and-mouth disease virus: Efficiency through exosites

Viruses were shown to encode proteinases in the 1970s. Initially, it was assumed that they would be only used for proteolytic processing of the viral proteins. Subsequent investigations showed that such proteinases could affect host metabolism to benefit viral replication. The foot-and-mouth disease virus (FMDV) leader proteinase (Lb pro ) cleaves several specific cellular targets. This mini-review summarises the cellular targets of Lb pro and illustrates the protein interactions away from the canonical substrate binding sites that Lb pro has evolved to enable specific and efficient cleavage of host proteins to promote FMDV replication. • The FMDV leader proteinase (Lb pro ) has an unusual cleavage specificity. • Lb pro cleaves the viral polyprotein as well as several cellular targets. • The cellular proteins eIF4G and ISG15 are rapidly cleaved during infection. • Efficient cleavage on eIF4G and ISG15 requires exosites on Lb pro . • Lbpro is a paradigm for the investigation of viral proteins of unknown function.