Convergent evolution in the mechanisms of ACBD3 recruitment to picornavirus replication sites

Author summary Enteroviruses are the most common viruses infecting humans. They cause a broad spectrum of diseases ranging from common cold to life-threatening diseases, such as poliomyelitis. To date, no effective antiviral therapy for enteroviruses has been approved yet. To ensure efficient replication, enteroviruses hijack several host factors, recruit them to the sites of virus replication, and use their physiological functions for their own purposes. Here, we characterize the complexes composed of the host protein ACBD3 and the ACBD3-binding viral proteins (called 3A) of four representative enteroviruses. Our study reveals the atomic details of these complexes and identifies the amino acid residues important for the interaction. We found out that the 3A proteins of enteroviruses bind to the same regions of ACBD3 as the 3A proteins of kobuviruses, a distinct group of viruses that also rely on ACBD3, but are oriented in the opposite directions. This observation reveals a striking case of convergent evolutionary pathways that have evolved to allow enteroviruses and kobuviruses (which are two distinct groups of the Picornaviridae family) to recruit a common host target, ACBD3, and its downstream effectors to the sites of viral replication.