Unveiling the Physico-Chemical Interactions, Structure, and Mechanics of Viral Genome Compaction: From Virus to Host Cell Environments

We provide a powerful physio-chemical approach illuminating the role of large mechanical forces involved in the entire journey of the viral genome, from its ejection into host cells, formation of viral replication condensates (RC) in cells, to packaging during virion assembly.

We merge structural and mechanical interrogation of viral genome condensates in viruses and cells, through a unique platform based on X-ray and neutron scattering analysis and bio atomic force microscopy.

We discovered that dense DNA packing creates immense pressure inside herpesvirus capsids, driving ejection of viral genome into the host nucleus.

This process, and subsequent viral RC formation, suggest a novel virus-induced cell mechano-protection mechanism crucial for viral replication and the integrity of nuclear structures, which will be investigated in this proposal.

Viral RC formation modulates chromatin organization, thereby impacting both functional (e.g. gene expression) and physical (e.g. mechanical stiffness) properties of the nucleus.

Our aim is to investigate the consequences of viral infection on the functional organization of the nuclear periphery and how these changes modulate the viral replication.

While herpesviruses are our main experimental system, we seek to establish a universal platform for the identification of pressurized genomes in other viruses as a gateway to devising genome-condensing antivirals for each virus with a pressurized genome. This project will take four years.