Liquid-liquid phase separation enables highly selective viral genome packaging

TL;DR

This study demonstrates that liquid-liquid phase separation in viruses enhances the selectivity and efficiency of viral genome packaging, providing insights into viral assembly and potential bioengineering applications.

Contribution

The paper introduces models showing how viral condensates improve genome packaging selectivity and efficiency, revealing a new mechanism in viral assembly.

Findings

Condensates increase assembly rates and yields significantly.

Selectivity is enhanced when capsid proteins are translated during assembly.

Viral condensates could be exploited for selective encapsulation in engineered systems.

Abstract

In many viruses, hundreds of proteins assemble an outer shell (capsid) around the viral nucleic acid to form an infectious virion. How the assembly process selects the viral genome amidst a vast excess of diverse cellular nucleic acids is poorly understood. It has recently been discovered that many viruses perform assembly and genome packaging within liquid-liquid phase separated biomolecular condensates inside the host cell. However, the role of condensates in genome packaging is poorly understood. Here, we construct equilibrium and dynamical rate equation models for condensate-coupled assembly and genome packaging. We show that when the viral genome and capsid proteins favorably partition into the condensate, assembly rates, yields, and packaging efficiencies can increase by orders of magnitude. Selectivity is further enhanced by the condensate when capsid proteins are translated during assembly and packaging. Our results suggest that viral condensates provide a mechanism to ensure robust and highly selective assembly of virions around viral genomes. More broadly, our results may apply to other types of selective co-assembly processes that occur within biomolecular condensates, and suggest that liquid-liquid phase-separated condensates could be exploited for selective encapsulation of microscopic cargo in human-engineered systems.