Viruses are obligate intracellular parasites entirely reliant on host translation machinery to produce their proteins. This dependency drives a constant evolutionary arms race, where viruses hijack host translation pathways, and hosts evolve countermeasures. Enteroviruses typically hijack host translation by using their 2A protease to cleave the host initiation factor eIF4G. This effectively shuts down host protein production while simultaneously allowing continued viral translation.   Here, we have investigated how interactions between viral proteases and host translation machinery shaped the evolution of swine vesicular disease virus (SVDV), a porcine enterovirus that emerged after a human-to-pig species jump from Coxsackievirus B5 (CVB5) a human enterovirus. The high number of mutations in SVDV’s 2A protease suggests it was critical for cross-species adaptation. Sequence differences identified in the human versus porcine eIF4G1 cleavage sites suggest 2A adapted to its new host target.  We have investigated the efficiency with which CVB5 and SVDV cleave human and porcine variants of eIF4G1, assessing the impact on host cell shutoff in human and porcine cells. We used structural modelling to investigate how 2A adaptations affect these interactions. This work advances our understanding of the molecular mechanisms viruses use to fine-tune host machinery to adapt to new species, offering critical insights into future species-jump events.