PT  - JOURNAL ARTICLE
AU  - Jia Yi
AU  - Jessica Morel
AU  - Mickaël Costallat
AU  - Nathalie Lejal
AU  - Bernard Delmas
AU  - Christian Muchardt
AU  - Eric Batsché
TI  - Influenza A virus RNA Polymerase targets the chromatin of innate immune response genes
AID  - 10.1101/2022.03.30.486363
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.03.30.486363
4099  - http://biorxiv.org/content/early/2022/03/31/2022.03.30.486363.short
4100  - http://biorxiv.org/content/early/2022/03/31/2022.03.30.486363.full
AB  - The influenza A virus (IAV) profoundly affects host cell nuclear processes to accommodate for its transcription. In particular, the IAV RNA polymerase (FluPol) associates with host genes to snatch capped 5’-ends from nascent messenger RNAs, that are then used to prime viral transcription. The extend of FluPol-host gene interaction and its actual consequence on host transcription are still poorly characterized. We show here, using genome-wide approaches, that the PA, PB1, and PB2 subunits of FluPol establish contacts with both chromatin and RNA transcripts at promoters, but also within the coding region of genes. These interactions also reach into downstream regions where recruitment of FluPol subunits correlates with previously reported transcription termination defects induced by IAV, indicative of an implication of the FluPol in this viral strategy to limit host cell defense by interfering with transcription re-initiation. The latter is further suggested by a bias in the FluPol genomic targets, enriched in genes associated with anti-viral defense. Together, our observations suggest that FluPol-chromatin binding contributes to targeted dampening of host immune response pathways.Competing Interest StatementThe authors have declared no competing interest.