Invité direction: Nadia Naffakh, Institut Pasteur, Paris -« Hijacking the host: cellular co-factors in influenza A virus transcription and replication »

Résumé

This seminar will focus on how influenza A viruses co-opt essential host factors to coordinate transcription and replication of the viral genome, with particular emphasis on cellular RNA polymerase II (Pol II), ANP32A and TDP-43.
The viral polymerase (FluPol) associates with the cellular Pol II, which enables it to « steal » 5′-capped ends from nascent Pol II transcripts and to use them as primers to initiate the transcription of viral mRNAs, in a process known as « cap snatching ». New insights into the mechanism of co-transcriptional cap snatching by FluPol, obtained in collaboration with structural biologists in the S. Cusack and P. Cramer laboratories, will be presented.
Our data suggest that binding of FluPol to the disordered C-terminal domain of Pol II provides an anchor not only for viral transcription but also for genome replication. The balance between these two activities, and the interplay among FluPol, Pol II and ANP32A – which stabilizes FluPol in an asymetric replicase-encapsidase dimeric conformation – will be discussed.
Finally, I will present evidence that FluPol recruits cellular transcription factors, notably TDP-43, and orchestrates the assembly of viral mRNPs.