[1] The primer activity of VPg occurs when the protein becomes uridylated, providing a free hydroxyl that can be extended by the virally encoded RNA-dependent RNA polymerase.
3Dpol (the RdRp) is able to synthesize VPg-pUpU-OH by using a polyA sequence within a stem-loop structure (cis-acting replication element) of 2C-ATPase as a template.
[5][6][7] Furthermore, a 5' terminal cloverleaf is required in cis to form the 3Dpol preinitiation RNA replication complex involved in uridylylating VPg.
[10] Because VPg sits at the 5' end of the genome, similar to eukaryotic 5' mRNA caps, several experiments were performed to explore its function in translation.
Poliovirus utilizes an internal ribosome entry site (IRES) instead of a cap for translation initiation, abrogating the requirement of VPg in initial infection[11] whereas studies with feline calicivirus confirmed that the VPg protein interacts directly with the cap-binding protein of the ribosome, eIF4E, and that this interaction is essential for viral translation.