VPg, a 22 amino acid long viral protein, is covalently linked by the tyrosine hydroxyl to the 5′ terminus of viral RNA via a phosphodiester (Ambros and Baltimore, 1978). There are four distinct cis-active RNA sequences and structures required for RNA replication: a cloverleaf RNA sequence and structure at the 5′ terminus (5′ CL), a cis-replication element (CRE) in the open reading frame, a 3′ nontranslated region (3′ NTR), and a 3′ poly(A) tail.