PRJNA727026
Suv4-20h2 protects from influenza virus infection through suppression of chromatin loop structure
The spatial organization of chromatin is known to be highly dynamic in response to environmental stress. However, it remains unknown how chromatin dynamics contributes to or modulate the disease pathogenesis. Here we show that upon influenza virus infection, H4K20me3 methyltransferase Suv4-20h2 binds the viral protein NP, which results in the inactivation of the Suv4-20h2 and the dissociation of cohesin from Suv4-20h2. Inactivation of Suv4-20h2 by virus infection or genetic deletion, leads to active loop formation at HoxC8-HoxC6 through the loading of cohesin to this region. HoxC8 and HoxC6 in turn enhance viral replication by inhibiting the Wnt-beta-catenin mediated interferon response. Importantly, loss of Suv4-20h2 augments the influenza pathology in vivo. Thus, Suv4-20h2 acts as a safeguard against influenza virus infection though the suppression of a cohesin-mediated loop formation.