Pre-existing genome architecture partitions viral takeover in the smallest free-living eukaryote

Nuclear DNA viruses colonize host genomes that are already organized into complex spatial domains within the smallest free-living eukaryote, Ostreococcus tauri. However, whether such established spatial boundaries determine the progression of viral takeover has not been fully understood, possibly due to the intertwining of sequence composition and transcriptional output in animal models.

To address this, researchers tracked the productive lytic infection of Ostreococcus tauri by the giant double-stranded DNA prasinovirus OtV5, monitoring transcription, accessibility, and three-dimensional contact dynamics across parallel time courses.

Despite a 18-fold collapse in total cellular transcript pools by 10 hours post-infection, the host's transcriptional shutdown, decay of insulation, early chromatin opening, and viral DNA positioning were all confined to spatial coordinates that were established prior to viral arrival. In particular, two low-GC outlier domains experienced a rapid surge in chromatin accessibility, with the insulation eroding and loci showing relative upregulation within 6 hours post-infection.

Importantly, the smaller outlier region maintained higher transcript levels per cell compared to the rest of the genome.

A surprising finding was that viral DNA was preferentially depleted from these accessible outlier cores, with instead contact made by the standard-GC telomeric flanks situated immediately beyond the pre-existing spatial boundaries. This suggests that domain identity, rather than local accessibility or active host expression, governs viral positioning within the host cell.

These results demonstrate that pre-existing nuclear architecture plays a crucial role in partitioning both the physical and transcriptional takeover of the host cell by the virus.