The Picornaviridae is a large and diverse family of non-enveloped (+)ssRNA viruses responsible for a wide array of diseases, both in humans and animals, such as hepatitis A, common cold or poliomyelitis. Once in the cell, the viral genome is translated into a large polyprotein, further cleaved, thanks to viral proteases, into functional viral proteins. Among these, the 2A protein was described as the most diverse in size and function. Interestingly, several picornavirus genera, such as Parechovirus, Kobuvirus, Avisivirus and Tremovirus, share sequence homology with the non-essential human phospholipase and acyltransferase PLAAT3, a host factor for some picornaviruses. In their N-terminal domain (NTD) lays the conserved H-box and NC-motif, which are part of the catalytic triad and essential for PLAAT enzymatic activity. The C-terminal domain (CTD) appears hydrophobic and is essential for the catalytic activity as well as the cellular localization of PLAAT3. This host factor participates at an early stage of the viral life cycle by facilitating the genome transfer from the virus particle to the cytoplasm. Evolutionary pressure on the viral genome and the size constraint from the capsid forces the virus to only carry essential protein sequences for infection. This suggests that these viruses may have acquired the 2A^H/NC protein through adaptation and evolution, to become partially or totally independent of PLAAT3.

This thesis investigates the relationship between structures and functions from several representatives of the Picornaviruses supergroups, with a particular focus on Aichivirus A1 (AiV-A1), Tremovirus A (AEV-2A), Turkey Avisivirus (AsV-A1) and the Parechovirus genus. Understanding the structural and functional diversity of the 2A^H/NC proteins will give a better insight into their roles in the viral life cycle and the molecular mechanism behind the potential bypass of PLAAT3.