Dynamic changes in host genome 3D structure in response to influenza virus infection

Abstract

Genome is spatially organized in the nucleus. The chromatinized DNA segregates into an active "A" compartment, which contains gene-dense chromatin bearing active epigenetic marks, and an inactive "B" compartment, which contains gene-poor chromatin bearing repressive epigenetic marks. Compartments represent the long-distance interaction patterns including topologically associating domains (TADs) and lamina-associated domains (LADs). Influenza virus replicates its genome in the nucleus and viral proteins have shown to interact with multiple components of the host epigenetic machinery to promote viral replication and limit host immune responses. However, it is unknown how influenza virus infection can affect the spatial configuration of chromatin and function of the host genome in the nucleus. In the present study, using genome-wide chromosome conformation capture (Hi-C) technique we showed the dynamic changes in TADs and A/B formations during the course of influenza virus infection in mouse embryonic fibroblasts. In addition to nuclear lamina disruption, DamID-seq demonstrated the changes in LADs formation following virus infection. Thus, our data suggest dynamic changes in host genome 3D structures to virus infection, which could be a novel therapeutic target for influenza virus infection.