Viral RNA polymerase
The influenza virus RNA-dependent RNA polymerase, composed of polymerase basic 1 (PB1), polymerase basic 2 (PB2) and polymerase acidic (PA) subunits, transcribes and replicates the segmented viral RNA (vRNA) genome in the nucleus of the host cell (te Velthuis and Fodor 2016; Fodor and te Velthuis, 2019). Transcription by the viral polymerase results in capped and polyadenylated mRNAs and involves the cap-snatching activity of the polymerase. Transcription is performed in close association with host RNA polymerase II (Walker and Fodor 2019). Replication by the viral polymerase proceeds through a complementary RNA (cRNA) replicative intermediate which serves as template for the synthesis of genomic vRNA.
In collaboration with Jonathan Grimes’ group we solved the first complete structures of medically relevant human and avian influenza A viruses (Fan et al 2019) as well as the structure of the human influenza C virus polymerase (Hengrung et al 2015; Serna Martin et al 2018). Our structural work, combined with functional studies, provides insights into the molecular mechanisms of transcription as well as replication. Our data show that the influenza virus RNA polymerase is a highly flexible macromolecule that is able to assume different conformations upon binding to various viral and cellular factors. It is this high flexibility that underpins the multifunctional nature of the influenza virus polymerase complex that is capable of primer-dependent transcription a well as primer-independent replication.
Watch the conformational rearrangement of the influenza virus polymerase upon vRNA promoter binding here.