English: Initiation modes for RNA synthesis during calicivirus replication. (A) The synthesis of antigenomic RNA results in the formation of a double-stranded RNA intermediate; antigenomic RNA synthesis is initiated in a VPg-dependent manner or de novo. (B) The synthesis of new genomic RNA was described to start either de novo or from a poly(C) stretch of nucleotides that were added by the RdRp’s terminal transferase activity. (C) The synthesis of subgenomic RNA may be initialized internally using a stem loop in the negative-sense antigenomic RNA and VPg priming; according to an alternative mechanism, a premature termination of antigenomic RNA synthesis results in anti-subgenomic RNA that is then used as a template for subgenomic RNA synthesis, a process that is suggested to involve a poly(C) stretch similar to the proposed initiation of genomic RNA synthesis. (D) Overview of the various mechanisms that were postulated for the initiation of calicivirus RNA synthesis. Green and black lines symbolize negative- and positive-sense RNAs, respectively; the loop in negative-sense RNAs indicates the position of a stem loop that may act as a subgenomic promoter region; dashed arrows indicate the initiation point and direction of RNA synthesis; hexagons represent VPg proteins that are covalently bound to the 5′ end of all positive-sense RNAs; pG indicates guanylation; An, Un, and Cn represent poly(A), poly(U), and poly(C) sequences, respectively.