Written by Charlotte Harrison, Science Writer
Viruses hijack host cellular processes to replicate and produce infectious progeny. But little is known about how a viral nucleic acid gets inside a particle. Now, a study published in Nature shows that viral proteins use a process known as phase separation to coordinate the assembly of progeny particles.
It’s all about BMCs
Biomolecular condensates (BMCs) are membraneless assemblies that compartmentalize cellular proteins and nucleic acids in distinct subcellular environments. They are formed by phase separation, a process in which a single phase of a particular biomolecule separates into a condensed phase and a dilute phase.
The role of BMCs in organizing and regulating cellular processes indicates that many viral subcellular compartments might be BMCs formed by phase separation. To investigate the role of BMCs during viral infection, the authors of the study took advantage of the tractability of human adenovirus – a nuclear-replicating DNA virus. Adenovirus proteins involved in genome replication are distinct from those involved in particle assembly and genome packaging, so the authors reasoned this property would enable them to use genetic approaches to untangle the role of phase separation in specific viral processes.
The 52kDa protein controller
The researchers demonstrated that a dedicated assembly/packaging protein — the adenovirus 52kDa protein — makes BMCs through phase separation and co-ordinates the assembly of new infectious particles. They showed that the 52kDa protein organizes viral capsid proteins into nuclear BMCs, and this organization is essential for the assembly of complete, packaged particles containing viral genomes.
“Our findings suggest that the viral particle forms around the viral genome …[and] phase separation allows this process to occur in an orderly, coordinated fashion,” said lead author Matthew Charman in a press release.
The authors then honed in on features of the 52kDa protein that contribute to phase separation. Here, they showed that specific amino acid residues in the intrinsically disordered region of the 52kDa protein govern phase separation and the dynamic nature of BMCs.
The authors proposed model in which BMCs regulate viral assembly gives us a better understanding of the complex viral assembly processes that underlie how DNA viruses replicate.
“Understanding how viruses are made opens up a world where we could not only potentially target those viruses more effectively…but also create gene therapy tools that lack the limitations of current delivery approaches,” noted Charman.