The molecular anatomy of influenza virus RNA polymerase.

The genome of influenza virus is composed of eight RNA segments of negative polarity. The RNA-dependent RNA polymerase is associated with each viral RNA (vRNA) segment and in virus-infected cells, involved in both transcription, i.e. vRNA-directed synthesis of viral mRNA, and two step reactions of vRNA replication, i.e. vRNA-dependent synthesis of complementary RNA (cRNA) and cRNA-dependent synthesis of vRNA. The RNA polymerase is composed of three viral proteins, PB1, PB2 and PA. PB1 is the core subunit for not only the RNA synthesis but also the assembly of PB2 and PA into this multifunctional enzyme complex. PB1 alone is able to catalyze vRNA-dependent RNA synthesis, but PB2 is required for capped RNA-dependent transcription, both together forming the transcriptase. The third P protein, PA, and an as yet unidentified host factor(s) are involved in the conversion of RNA polymerase from transcriptase to replicase. The functional map is being made for both PB1 and PB2 proteins.