Protein-primed initiation of RNA replication (=VPG capping)

Initiation of transcription/replication occurs via a protein primer-dependent mechanism. The protein linked in 5'-genomic RNA is called VPg (viral protein genome-linked) and replaces normal capping. In this way, recognition of viral 5' RNA by host antiviral receptors can be bypassed, and in some cases it replaces the cap function initiation of translation.

Enzymatic reaction:
Protein-primed terminal nucleotidyl transferase: RNA-dependent RNA polymerase (RdRp) attaches one or more nucleotides to a Tyrosine or asparagine in the target protein through a nucleotidyl-transferase reaction (Nucleotidylylation).

Picornavirus VPG can be removed by cellular TDP2/VPg unlinkase . This would enhance viral replication, but it is not clear why it does not elicit a RIG -like receptors (RLR) antiviral response. It is possible that removal of VPG in the dsRNA replication intermediate would make more VPG available for transcriptoin, since this protein is limited and produced only once per polyprotein.