Interplay between Influenza Virus and the Host RNA Polymerase II Transcriptional Machinery

The influenza virus RNA-dependent RNA polymerase (RdRP) cleaves the 5′ end of nascent capped host RNAs and uses the capped RNA fragment to prime viral transcription in a mechanism called ‘cap snatching’. Cap snatching requires an intimate association between influenza RdRP and cellular RNA polymerase II (Pol II), which is the source of nascent capped host RNAs targeted by influenza virus. Recent structural studies have revealed how influenza RdRP binds to Pol II and how this binding promotes the initiation of viral transcription by influenza RdRP. In this review we focus on these recent insights into the mechanism of cap snatching by influenza virus and the impact of cap snatching on host gene expression during influenza virus infection. Influenza virus RdRP associates with cellular Pol II. This provides influenza RdRP with a source of nascent capped host RNAs which it targets in a process called ‘cap snatching’ to generate primers for viral transcription. Influenza RdRP makes direct interactions with the Pol II C terminal domain (CTD). Molecular details of these interactions have recently been determined, and there is evidence that Pol II CTD binding promotes viral transcription by modulating the conformation of influenza RdRP. Influenza RdRP cap snatches small nuclear/nucleolar RNAs most frequently. When cap snatching generates suboptimal capped RNA fragments, influenza RdRP can use a prime-and-realign mechanism to promote transcription initiation. Influenza virus infection reduces Pol II abundance in gene bodies, suggesting that cap snatching contributes to host shut-off.