AUF1 p45 promotes West Nile virus replication by an RNA chaperone activity that supports cyclization of the viral genome

A central aspect of current virology is to define the function of cellular proteins (host factors) that support the viral multiplication process. This study aimed at characterizing cellular proteins that assist the RNA replication process of the prevalent human pathogen West Nile virus (WNV). Using in vitro and cell-based approaches, we defined the p45 isoform of AU-rich element RNA-binding protein 1 (AUF1) as a host factor that enables efficient WNV replication. It was demonstrated that AUF1 p45 has an RNA chaperone activity, which aids the structural rearrangement and cyclization of the WNV RNA that is required by the viral replicase to initiate RNA replication. The obtained data suggest the RNA chaperone activity of AUF1 p45 is an important determinant of the WNV life cycle.