Ezrin-Radixin-Moesin Family Proteins Are Involved in Parvovirus Replication and Spreading

The propagation of autonomous parvoviruses is strongly dependent on the phosphorylation of the major nonstructural protein NS1 by members of the protein kinase C (PKC) family. Minute virus of mice (MVM) replication is accompanied by changes in the overall phosphorylation pattern of NS1, which is newly modified at consensus PKC sites. These changes result, at least in part, from the ability of MVM to modulate the PDK-1/PKC pathway, leading to activation and redistribution of both PDK-1 and PKC eta. We show that proteins of the ezrin-radixin-moesin (ERM) family are essential for virus propagation and spreading through their functions as adaptors for PKC eta. MVM infection led to redistribution of radixin and moesin in the cell, resulting in increased colocalization of these proteins with PKC eta. Radixin was found to control the PKC eta-driven phosphorylation of NS1 and newly synthesized capsids in vivo. Conversely, radixin phosphorylation and activation were driven by the NS1/CKII alpha complex. Altogether, these data argue for ERM proteins being both targets and modulators of parvovirus infection.