FIGURE 10.

Our model of influenza genome replication initiation. vRNA → cRNA replication initiation is shown as follows. First, an additional nucleotide (in italic type) is added to the 3′-end of vRNA by the RNA-specific ribonucleotidyltransferase of the host. Influenza RdRp initiates replication from the U at −2 and reads through to the UUUU (primary replication). The dinucleotide AG produced from the resultant cRNA can then be used for replication initiation (secondary replication). cRNA → vRNA replication initiation is shown as follows. The replication initiation from cRNA starts from U(−4)C(−5) (22). The dinucleotide AG (in boldface type), which is synthesized from U(−4)C(−5), is released from the template because RdRp becomes stuck at the underlined U (−6) of UUU (−6 to −8), as in polyadenylation at the U stretch of the 5′-end of vRNA (40), and is then relocated to the 3′-end of cRNA to allow it to read through the UUU.